Diabetes --Mange yourselves

Boycott diabetologists !! Why  we the gynecologist can’t treat  GDM or DM by ourselves.?

Part I: What are the different degrees of  abnormal glucose metabolism?  Q. 1:  How to diagnose  frank DM ?? What are the criteria for diagnosis of frank diabetes??

Grades of abnormal GLUCOSE METABOLISM? What are the different types of  impairment of glucose metabolism ?? For  men & non pregnant woman what is frank Diabetes?? What is IFG(impaired fasting glucose) , Impaired PP sugar ( impaired isolated PP sugar) , or IGTT(both FBS & PPBS are abnormal but do not quantify for DM to that extent). . GTT becomes an  unnecessary for diagnosing frank DM   ?? Ans:-All values mentioned under are the diagnostic criteria of frank DM e.g. Such  are venous plasma true glucose values( random ) > 200 mg % is  sufficient to make diagnosis  of diabetes. However the diagnostic criteria for glucose metabolic abnormalities taken together are as follows   three kinds of abnormalities  for 1) frank diabetes , 2)  IFG and 3)  IGT .

A)                      In a person with classical symptoms of diabetes, as mentioned earlier  one reading  of unequivocal  hyperglycemia i.e.  random venous plasma   glucose > 200 mg % is  sufficient to make diagnosis  of diabetes. For  example   if a person has polyuria  , polydipsia,  weight loss and random blood  glucose is   of 278 mg%  he/ she is diabetic  and no other   test is required to confirm  the diagnosis . In such a situation he/ she should be treated with a consulation with a  diabetologists or else treated by local doctor with 1) diet control b)  Exercise and in  phases 3) Oral antidiabetic agents like metformins, gliptins .

B)                      Fasting only > 126 on two occasions? What will be  medical diagnosis of such glucose metabolism diosrder??   Ans: This is also to be treated as frank DM. For instance,  imagine a condition where fasting venous plasma glucose is 126 mg % on more  than one occasion-à  then too  he /she  should  also be  considered as  frank DM . Such a figure  is  sufficient for diagnosis  of diabetes  even in the absence   of symptoms and no PP sugar estimation is essential for confirmation of frank DM,..

C)                     A two hour venous plasma glucose  of 200 mg %   or more,  after oral  glucose   load of 75 g  on more  than one occasion is frank  DM

 Q. 2:- What is isolated IFG?? Ans: If fasting  venous plasma glucose level is between 100 to 126 mg% .Bit  in this case impaired fasting glucose tolerance(IFT) there is a precondition that

two hours  post 75 g glucose  venous plasma glucose  level must be  below  140 mg % .Then only  the  condition is called  impaired fasting glucose tolerance(IFT).  .Therefore in summary  “impaired fasting glucose tolerance implies , in nondiabetic  persons fasting is slightly raised and 2 hours  post oral  75 Gm  glucose  values  of venous plasma glucose  are in the range of  100 mg% to-125 mg%  but PPBS is <  140  mg%   respectively then it is called  IFG.

Q. 2B: (IGT) .By contrast impaired PPBS means isolated rise of PPBS while FB glucose is normal,(IGT) .

 IFT /IGT  are the   two conditions that represent an intermediary state between   normal on one side and diabetes on the other side  .

Q.3:- Why such classification ? What is the relevance ?  Ans:. Some   people have isolated IFG/IGT as separate entities and have planned diet accordingly   while others have combined IFG  and IGT as prediabetes .  As regards micro vascular   complications   of diabetes people in IFG   and IGT  are not at significant   risk  and in this respect both the conditions are equivalent. However as regards macrovascular   diseases associated with diabetes people in IGT(where PPBS is high isolated)  are at a higher risk  as compared  to those in IFG

All about Diabetes:-Q.4: What action should be taken to minimize macrovascular   diseases associated with diabetes people in IGT(isolated PPBS is high with normal FBG)  ?? .Then what to do-?? How the person concerned   can minimize vascular diseases??  Ans:-With a) control of weight with prudent diet and b) physical   exercise   . Approximately 50% people with IGT (borderline high PPBS with normal or subnormal even FB glucose)   revert back to normal.  Some remain   in IGT range while others slip into clear diabetic range over a course of time.

Q.5:- What  is the progression rate of IGT (isolated  rise of PP glucose) to Frank DM per year??  Ans:-On an average every year 5% of people with IGT group will proceed to Frank DM per year.  There is no urgency to put all IGT on OAD(oral antidiabetic in a hurry)   .Instead    they(IGT)  need proper diet control exercise and six monthly follow up with blood glucose estimation. Those who are unlikely to follow diet and exercise regimen can be   put on metformin or acarbose. will be welcome by all All about Diabetes:-Q.4: What action should be taken to minimize macrovascular   diseases associated with diabetes people in IGT(isolated PPBS is high with normal FBG)  ?? .Then what to do-?? How the person concerned   can minimize vascular diseases??  Ans:-With a) control of weight with prudent diet and b) physical   exercise   . Approximately 50% people with IGT (borderline high PPBS with normal or subnormal even FB glucose)   revert back to normal.  Some remain   in IGT range while others slip into clear diabetic range over a course of time.

Q.5:- What  is the progression rate of IGT (isolated  rise of PP glucose) to Frank DM per year??  Ans:-On an average every year 5% of people with IGT group will proceed to Frank DM per year.  There is no urgency to put all IGT on OAD(oral antidiabetic in a hurry)   .Instead    they(IGT)  need proper diet control exercise and six monthly follow up with blood glucose estimation. Those who are unlikely to follow diet and exercise regimen can be   put on metformin or acarbose. .4: What action should be taken to minimize macrovascular   diseases associated with diabetes people in IGT(isolated PPBS is high with normal FBG)  ?? .Then what to do-?? How the person concerned   can minimize vascular diseases??  Ans:-With a) control of weight with prudent diet and b) physical   exercise   . Approximately 50% people with IGT (borderline high PPBS with normal or subnormal even FB glucose)   revert back to normal.  Some remain   in IGT range while others slip into clear diabetic range over a course of time.

• Q.5:- What  is the progression rate of IGT (isolated  rise of PP glucose) to Frank DM per year??  Ans:-On an average every year 5% of people with IGT group will proceed to Frank DM per year.  There is no urgency to put all IGT on OAD(oral antidiabetic in a hurry)   .Instead    they(IGT)  need proper diet control exercise and six monthly follow up with blood glucose estimation. Those who are unlikely to follow diet and exercise regimen can be   put on metformin or acarbose s

- HBA1C is the best guide .How authentic / representative is blood glucose estimation?? Does it (results) vary from one lab to another lab?? What was the recommendations and conclusion of International Committee American Diabetes Association’s annual Congress in June 2009 in this regard??

One will be surprised to know that:-

1)                   At present there is no single gold standard test for the diagnosis of diabetes.

2)                   The measure to capture chronic exposure to glucose (HBA1C) is more likely to be informative about presence of diabetes than single measure of glucose!!!! But we usually avoid this tests for cost factor.

3)                   Tip on HBA1C :-Know this parameter in details.  What we need to know & remember on HBA1c .

4)                    For Chr diabetics HbA1c is a reliable measure of  chronic hyperglycaemia  and has  a better co relationship  with  chronic micro vascular complications. DM by itself do not kill a person .It is vascular complications (H attack, thrombotic stroke or nephropathy (CKD & repeated dialysis) which are the prime cause of death.

5)                     HbA1c estimation has to be done by the right way which is seldom done in India. It has to be   done by  the method certified by  NSGP has several advantages  over blood glucose estimation

6)                    I hope many of us are aware of the fact that  a properly performed HbA1c  is a better test for diagnosis of diabetes than blood glucose estimation .

7)                   Diagnosis of diabetes is made if HbA1c  is equal to or greater than 6.5%

8)                   Diagnosis of diabetes should be confirmed by repeat  HbA1c  estimation unless there are gross symptoms of diabetes and random blood glucose is above  200 mg% (again cost factor and ? harassment of the person concerned)

9)                   In those  suffering from  haemoglobinopathies and anemia interfering with HbA1c  estimation and interpretation and if HbA1c  estimation is not available current conventional tests should be used for the diagnosis of diabetes

10)          In pregnancy blood glucose estimation should be  continued to be used for  the diagnosis of diabetes   as changes accruing in red cell turnover rate during the pregnancy can affect HbA1c  estimation

11)          Individuals with HbA1c values between 6.0 to 6.5% are likely to have higher risk for progression to diabetes  and thus should be kept on follow up ans screened for other risk  factors.

12)          Tip   on diagnosis & Tr of diabetes? What did the “American Diabetes  Association ratified the recommendations of the  International  committee “ ??  American Diabetes  Association in January 2010 ratified the recommendations of the  International  committed as regards the use of HbA1c  for the  diagnosis of diabetes mellitus in its position statement issued in supplement to Diabetes Care .

Tip 13:- What about India? Why we have not shifted from traditional glucose estimations to HBA1C?? Are we in India ready for adaptation of HbA1c  as a diagnostics test  for diabetes in non pregnant  persons? In many places and situations we are not yet ready because of the following reasons :--

1)                      Properly done HbA1c  test is available  only at limited laboratories in big cities/ towns .

2)                      The cost  of doing HbA1c is eight  times more than that  of blood glucose test thus it  would be  out of reach of majority of Indians.

3)                      Many GP doctors are not conversant with the interpretation of HbA1c report. However clinicians should be aware of this latest addition to the  diagnostic criteria   for diabetes and wherever possible  this new  criterion can be used

. Tip 13B_ More informants on  HBA1C:  How useful is Glycosylated Hemoglobin Estimation ??

This blood test is useful to estimate the average control of blood glucose in the previous 90 days. The blood can be drawn any time of the day. If done by a reliable laboratory it provides important information which  blood glucose   estimation cannot provide ideally it should be done at every three monthly follow up visit In addition to blood glucose estimation. The two values together give vital information.

For example :

1)                      Normal  HbA1c high FBS  interpretation overall control over the last 90 days was okay and it is possible that either control was lost  recently or the patient  did not take the previous evening’s  medication.  One should verify  before increasing  the dosage of medication  under   such circumstances.  Better not to augment the ODA(Oral anti diabetic ).

2)                       High HbA1c normal fasting  and post lunch blood  glucose:--In such cases it is easy to rpt PPBS only within few days. Some people take small working  lunch but a large dinner their  post dinner blood  glucose values  are much higher than post lunch blood glucose values .

3)                       

4)                      High  HbA1c   but normal blood glucose :--Interpretation overall  control over th last 90 days    was poor and control was achieved in the last  few days. If such results are obtained in peemployment check up one should suspect the possibility   of a diabetic   person hastily achieving control through   treatment   from a private doctor so as to pass the pre employment medical examination.

Estimation of  HbA1c has become an integral part of routine laboratory  tests in  day to day management of diabetes in  economically advanced   countries  and also in any centers  in our country. HbA1c  has very good co relation with  micro vascular complications  of diabetes. However  it has certain  limitations  which precludes it’s  widespread use in our  country  such as cost of estimation  and non availability  of standardization.

Q.14 Principles of HbA1c  test :

In circulating  blood  glucose is constantly  getting attached to hemoglobin through non enzymatic process. This attachment  is irreversible and percentage  of hemoglobin in glycated form  out of total  hemoglobin in circulation depends  upon blood  glucose level. Thus in  a diabetic  patient  depending on the degree of hyperglycemia over previous 90 days  higher percentage of hemoglobin  is glycated as  compared  to normal  percentage of hemoglobin is glycated as  compared  to normal  persons in who around  4% to 6%  of hemoglobin is glycated,. In other words   HbA1c levels are in the range of 4% to 6% in non diabetic normal persons. Thus  a diabetic  with persistent  poor control  will have  very high  level of HbA1c  while a diabetic  with persistent  tight blood glucose  control will have his HbA1c values  near those  for normal  persons.

All diabetics  should  aim to keep their HbA1c  constantly between 6.5% to 7% .

Haemoglobin A1c as a diagnostic test for diabetes mellitus. Are we ready for it ? 

Abnormal glucose metabolism and Micro & Macrovascular diseases: Daig & prevention:-Diabetes mellitus is a metabolic and vascular disease  with hyperglycemia  and specific micro vascular complications in those who are poorly controlled over  a long term  period as it characteristic features . However  there is no well defined  threshold  level of blood  glucose  beyond which  micro vascular  complications develop and below which  there is a  complete immunity  from complications. Thus fating venous plasma glucose   value of 126 mg %  and tow hours post 75g  oral glucose   load   value of 200 mg%  are somewhat arbitrary diagnostic  values for diabetes  mellitus. At present   for the want   of better diagnostic  test blood glucose  values are used as the only criteria for the diagnosis of diabetes  however these  have certain  limitations.

4)                       

i)                

Tip 15 on diabetes:--:--:-Diagnosis of Gestational   diabetes mellitus

Historically criteria for the diagnosis  of GDM have always  been intensely  debated  and more than one school of  thoughts   has always existed. We will bypass the details of these k debates   and rationales put forward by the various schools of  thoughts  and follow the  2010  recommendations of International  Association of Diabetes and Pregnancy  Study Groups Which   were adopted by American Diabetes in 2011

There are : Diagnosis k of GDM in Pregnancy Threshold values

GDM = one or  more values > threshold

In addition to the abovementioned method of diagnosis  of GDM , WHO definition is also  commonly followed in our country . As per WHO , GDM  id diagnosed  when 2 hours  post 75 g glucose  challenge plasma equals or exceeds 140 mg%

Do we know how to tets glucose in urine ?? Our forefathers knew that skill and we have lost that wisdom!! Urine glucose Tip 16 : Know about DM from these posts  & treat your pt by your own skill & wisdom:-Tr  on diabetes:--:-How to test urine glucose? Does it furnish any new in formations to us?? Limitations of urine glucose estimation

As regards urine glucose  estimation. It should  never be solely relied upon  for diagnosis of diabetes. It can only be used for getting a very rough   idea of control  on a day  to day  basis  provided the patient or  his physician interpreting the results  is thoroughly conversant with limitations and pitfalls.

While doing urine  tests observe the following

a)                      Use  the dry  strip method  which is  specific for glucose instead  of Benedict’s  test which  gives many false positive  results.

In order    to reduce the cost by 50%  cut the test strip  vertically  in two equal  halves

b)                      Ask the patient to  complet4ely empty the bladder 15 minutes before  the time of urine  estimation so that when   the second   sample is collected for estimation  freshly formed urine  is obtained . Such  urine glucose estimation will give a more  realistic idea  about the spot  blood  glucose value.

In many diabetics glucose is invariably  spilled over in urine during the post  prandial period but they can  still have  a normal fasting blood glucose  and absence   of urine  glucose   in fasting state. However    in such  patients  urine voided first  thing in the morning  is actually  a mixture  of urine  formed  over several  hours overnight and hence it can show  glycosuria   even though  urine actually formed  in the morning  does not contain  glucose. Hence  it is  important to always  collect  freshly voided urine  for glucose  estimation .

: Tip 16 : Know about DM from these posts  & treat your pt by your own skill & wisdom:-Tr  on diabetes:--:-How to test urine glucose? Does it furnish any new in formations to us?? Limitations of urine glucose estimation

As regards urine glucose  estimation. It should  never be solely relied upon  for diagnosis of diabetes. It can only be used for getting a very rough   idea of control  on a day  to day  basis  provided the patient or  his physician interpreting the results  is thoroughly conversant with limitations and pitfalls.

While doing urine  tests observe the following

c)                       Use  the dry  strip method  which is  specific for glucose instead  of Benedict’s  test which  gives many false positive  results.

In order    to reduce the cost by 50%  cut the test strip  vertically  in two equal  halves

d)                      Ask the patient to  complet4ely empty the bladder 15 minutes before  the time of urine  estimation so that when   the second   sample is collected for estimation  freshly formed urine  is obtained . Such  urine glucose estimation will give a more  realistic idea  about the spot  blood  glucose value.

In many diabetics glucose is invariably  spilled over in urine during the post  prandial period but they can  still have  a normal fasting blood glucose  and absence   of urine  glucose   in fasting state. However    in such  patients  urine voided first  thing in the morning  is actually  a mixture  of urine  formed  over several  hours overnight and hence it can show  glycosuria   even though  urine actually formed  in the morning  does not contain  glucose. Hence  it is  important to always  collect  freshly voided urine  for glucose  estimation .Examine not only glucose but    ketones too  in urine.

Tip 19 on diabetes –What are the usual investigations in diabetics and suspected diabetics??? :

For  the diagnosis  of diabetes one should order Fasting and Post  75 gm glucose   challenge venous  plasma   glucose . GTT is usually not required. One should  order fasting  and post  glucose  challenge  blood  glucose  tests  in the following  situations:

a)           Those having symptoms  of diabetes

b)          Those having  tuberculosis peripheral neuropathy hypertension coronary  artery  disease cerebro vascular  disease  peripheral vascular disease  eczema premature  cataract etc

c)           As   a pre operative check up

d)          Those above 40 years  as part of a routine  medical  checkup

e)          These  tests should be done  every  six months in those who  have pre diabetes  and every 3 months in those who are known diabetics provided they are  well controlled d In known diabetics instead of post glucose blood  glucose post meal blood glucose should be ordered. In the initial  period  and in those who have  unstable control   blood glucose  tests should be repeated  more frequently  whereas  in emergencies  such  as diabetic  ketoacidosis  hypoglycemic coma etc  blood glucose  should be done several  times  a day.

f) In a newly  detected diabetic  patient  the following  additional   baseline  investigations should be ordered

a)           Lipid profile

b)          Serum  creatinine

c)           Full urine  examination  and test for micro albuminuria if routine  urine exam  . shows absence   of albuminuria

d)          Electrocardiogram

Detailed  ophthalmic  check up  Tip 18 : Urinary ketones in DM::: Know about DM from these posts  & treat your pt by your own skill & wisdom:-Tr  on diabetes:--:- How & when to tets Urine examination  for ketones :

It is  very important to examine urine for ketones in certain  specific situations such as :

1)                      When  patient has excessive  thirst hunger  and urination

2)                      Whenever   there is  vomiting  with or without  deterioration  in general condition

3)                      Whenever  a diabetic is drowsy and urine is loaded with   glucose  and blood glucose  is above 250 mg% 

In above mentioned situations presence of ketones in urine indicates diabetic  ketosis  and the patient should be instructed to seek immediate  medical attention .

e)          Method for examination of ketones in urine  is simple  and essentially same as that for glucose  estimation . Many  companies  market  dry strips  for urine ketone  examination  e.g. Keto diastick , which is designed to simultaneously 

Tip 20  on diabetes evolution by markers of damage already dome by loom standing  untreated / uncontrolled  DM ??  A) Serum tests :- like Serum  creatinine, Dyslipidaemia, CRP,  ,,ophthalmic  check up and  urine   for micro & quantitative estimation albuminuria  should be repeated every year . Neurological evaluation essential yearly basis .If the patient  develops  proliferate  retinopathy. It should be further  evaluated with Flouroscein  aangiography and treated  with Laser photocoagulation  to prevent  blindness.

. Tip 20 to members of this Group:--For advancement of knowledge in diabetes. Treat your pts by yourself without referring to diabetologists as far as possible ,ore so iffy is poor and comes from a rural area. :-  when   a patient  develops  diabetic nephropathy his OAD should be reassessed and use of nephrotoxic drugs e.g. .Aminoglycoside antibiotics and NSAIDs should be avoided. Whenever a diabetic patient loses  control and in those who are difficult  to control from the beginning a thorough  search should be made for  occult  tuberculosis and other infections and X ray  chest and other  appropriate  investigations should be ordered. Whenever   a long standing   diabetic  gradually requires  lesser  dosage  of OAD  or Insulin or he goes into hypoglycemia  with  the same dosage  suspect  diabetic  nephropathy. .

Lets discuss micro vascular  complications of diabetics??  Q.16 :-  Among  the micro vascular  complications of diabetes diabetic retinopathy is the most extensively studied complication as regards  its co relationship  with  fasting and post  glucose   load blood glucose   values. Till 1997  fasting venous plasma  glucose and two hours post 75 g oral glucose load cut off point  for diagnosis of diabetes were 140 mg% and 200

Mg% respectively  . These points were based on symptoms  of  diabetes and not on risk for development of micro vascular  complications  Even though there is no clear cut threshold  blood glucose value for retinopathy some people with fasting  blood glucose values  between  126-140 mg% have  evidence  of early non proliferative diabetic retinopathy however retinopathy  is very rare in those having fasting venous  plasma glucose value below 126 mg% .

Do you know ??!!! Tip 16 : Know about DM from these posts  & treat your pt by your own skill & wisdom:-Tr  on diabetes What lamed mark event was there in 1997 regarding diagnosis of DM ?? In 1997  criteria for diagnosis  of diabetes based on fasting blood glucose were lowered  from 140 to 126  mg.  Moreover  fasting value of 126 mg% has better co  relation with post glucose  load  value of 200 mg%  as regards  micro vascular   complications  Even  though lowering  of diagnostic  fasting blood  glucose  value  was seen  as a definite  improvement  using blood glucose  values for diagnosis  of diabetes  still have some limitations

Q. 18: What are the limitations of FBS estimations??  1)  poor reproducibility due to analytical variance 2) need to remain in fasting state  for 8hours 3) false  lower values if the blood sample is not analyzed with  in 1 hour  due to glycolysis . Q, 20: What is meant by “National Glycohamoglobin standardization program Laboratory methods for estimation of Haemoglobin  A1c  and instruments used for estimation “ ?? Ans: These  have been standardized in the advance countries by National Glycohamoglobin standardization program 99% of the laboratories estimating HbA1c  are NSGP  certified in USA. HbA1c  values  are reproducible storage of  collected blood for few hours does not  lead to faulty estimation . In addition HbA1c  has a better co  relationship with micro vascular complications as compared to blood  glucose values. While   the former is an indicator of average  glycemic control over preceding 12 weeks the later gives  information  about glycemic control at the precise point of time of drawing glucose from the  body. Thus HbA1c  is relatively  unaffected  by acute stressful  conditions. Moreover blood for it estimation can be  drawn at any time of the day.

Tip 20 :  from Dr S K Pal  : Know about DM from these posts  & treat your pt by your own skill & wisdom:-Tr  on diabetes: Should we then consider  HbA1c   test as a diagnostic criteria of DM? What is going to be the  current and  future means  of diagnosing diabetes in non pregnant adults??   Ans;-    Considering  the above  listed advantage of using HbA1c   test some  diabetologists  in advanced  countries  are of the opinion  that it should be used  as an additional option for the diagnosis  of diabetes in non pregnant persons. In 2008  The American  Diabetes Association along with international Diabetes  Federation  and European  Society for study of Diabetes   had jointly set up a committee of experts   to study  the current and  future means  of diagnosing diabetes in non pregnant adults . The international committee’s  reports  was discussed in a symposium held during American Diabetes Association’s annual Congress in June 2009 and published in June 2009  issue of Diabetes Care.

How many of us are aware Fructosamine Test ??  : listen what Dr S K Pal what he has to say on thgis tests ? Ans: Fructosamine Test is not that helpful in day to day  clinical practice. I, Dr Pal don’t recommend to do such tests (Fructosamine    )which are insignificant.

Why dislike Fructosamine tests ?? Because though like HbA1c Fructosamine  is a blood  test in which glycated plasma proteins are measured and expressed as percentage of total plasma proteins but it(Fructosamine  ) gives  information  on average metabolic control  over the previous  two weeks it is not yet regularly  done in our country. It  is more  useful than HbA1c  to access metabolic  control during  pregnancy.

Treat DM women by yourself. Listen what Dr S K Pal has to say on the Advantages of HBA1c  over Fructosamine??   Point 1;-HBA1c derived average  glucose  a new patient  friendly concept  of expressing metabolic  control

Point 2  Glycosylated haemolglobin HbA1c   a gold standard in assessing metabolic control   is expressed in % value. The bad aspect of HBA1c??  a) Even though it is an indicator of average  blood glucose control since  the unit  of expression is to in mg%   and since the values are at variance with blood glucose    values the expression is not patient  friendly . Better at least for research work one can perform  continuous interstitial fluid  glucose  monitoring for 48  hours( like Holters)  every few months particularly who are on insulin pump. monitoring  seven times a day three  times a week for 4 months for 4  months In addition they were subjected to HbA1c   estimation 3 times at a central laboratory in Europe Participants also  underwent self capillary glucose. From this data average  glucose value was calculated and it’s  correlation with HbA1c  was worked out and a mathematical formula to convert HbA1c  in to average glucose  value  was developed Interstitial fluid values  were scaled up by 5% to derive capillary glucose values 

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: Listen what Dr S K Pal has to say on  rational & timely use   of Glucometer in family practice provided the paper strips are not out of stalk & her/his eye sight is normal!! Presence of an maid servant who can read English will beef immense help. The instrument warrants 2 yarely servicing.

In a day to day practice of a family physician or general duty medical officer he commonly  has to deal  with routine management   including dosage      adjustments and also  handle  emergencies in a diabetic patient . thus  a properly  functioning  glucometer  with all the accessories is a must for him both   in th clinic  and in emergency bag. Glucometer  is an essential to a clinician as a stethoscope blood pressure  apparatus  and a torch.

Applications  of glucometer in family  physician’s clinic

1)                      When  a patient  walks in with symptoms  suggestive of  diabetes. Even  though one should not  solely rely on glucometer  readings  when hyperglycemia is detected for value  will definitely  help in planning   of  further line of action including  the investigations

2)                      When a known diabetic visits the clinic for routine check  upon the eve of his departure  from the city  and thus does not have  a time for formal laboratory tests in near  future.

3)                      When  a known diabetic  attends the clinic with  symptoms which  may or may not be related to diabetes  and does  not have  a recent   laboratory  blood glucose  report.

4)                      On emergency visit. On the spot blood glucose  estimation  is a must  at  every emergency

Symptoms such as hunger palpitations sudden sweating giddiness etc could be due to hypoglycemia  Random blood glucose  on the spots  helps  to detect   or rule out hypoglycemia. In case   of hypoglycemia one should immediately correct  the low blood glucose level by serving a carbohydrate  snack  like biscuits or refined sugar  containing  liquids and subsequently   reduce dosage of his anti diabetic medications if required . In case in te patient is semi conscious or unconscious 50 ml of 25% glucose should  be injected intravenously . Hypoglycemia  in patients  on alpha  glucosidase  inhibitors should be treated by administering oral or intravenous  glucose as it does not respond to carbohydrate     snacks  or table sugar On the spot blood glucose   estimation with glucometer also helps to rule out hypoglycemia and think of alternative condition Sudden  sweating could be a symptom of acute myocardial infarction since   hypoglycemia is more common there  is a tendency in patients  to assume  that they are having hypoglycemia   and to consume two teaspoons of sugar every  10 minutes. In case of  heart attack it leads to late   diagnosis and loss of vital  time before the patient is admitted in intensive care  unit. Thus  timely on the spot blood  glucose estimation  can save  precious  time and   life as well as  lots of money  by avoiding delay  in hospitalization  in case  of serious  condition such as  acute myocardial infarction or other cardiac  emergencies or by avoiding  unnecessary hospitalization in case of simple  hypoglycemic episode.

How useful is glucometer in rural men & women who know how to read English words & figures??   Prompt  use  of glucometer  and swift appropriate  action in only one episode  will more  than compensate for  the entire investment   cost  of glucometer.

Equipment  required for home blood glucose monitoring 

1)          Reliable  glucometer

2)          Chemically treated   strips  compatible  with the meter

3)          Lancets or fine needles to  prick the finger for a drop of blood

4)          Cotton  swabs

5)          Methyl alcohol or medicated spirit.

Glucometer : It is small electronic  instrument which  analyzes the concentration of glucose in a drop  of blood  transferred on chemically treated plastic stick  from patient’s  finger. The strip is inserted  in a slot on the meter,. Glucometer  runs on batteries. Several  brands are available in our country.                 

The cost  of the meter  varies from Rs 850/ to Rs 3000/ For those with high consumption of strips  many companies  offer free glucometers. The high end meters  have additional  features such as  varying memory capacity to store  previous readings along  with   date   and time automatic calculation  and display of mean  blood glucose  value  of last 15 days warning  beep  and message  if the values are out  of range  on either  side facility to download  the readings to computer  coding free operations etc.

Once a drop of blood from finger after  a prick with the lancet or needle is deposited on the designated area on the plastic strip which  is  inserted in the slot on the meter  the blood glucose   value is digitally displayed on the meter  screen in  five to fifteen seconds. One plastic stick is required for each test . The cost of strip works  out to be  in the range  of Rs 14  -25/   depending upon the meter and the number of strips  purchased at a time. These strips are  available  in vials usually each vial contains 25  strips. They  have unopened expiry period of about 16 months and six  months after the seal is opened. The disposable lancets and needles cost approximately Res 1-4 the pain following finger prick particularly when spring loaded lancet device is used is minimal and easily bearable. All  meters come  with a spring loaded lancet  device at no extra cost.

Reliability of glucometer

More  than twenty five years have elapsed since  the introduction of glucometer   During this period technology  has been continuously updated and deficiencies found to earlier meters have been gradually overcome. The modern meters are reliable  provided one understands  and follows  the instructions mentioned in the manual stores  the strips  properly and avoids using outdated strips  . It must be noted  that  with glucometer  capillary whole blood is tested for glucose  while during  laboratory  test venous   plasma component  of blood is tested for glucose  While  in fasting   stage glucose  levels in capillary whole blood and venous plasma are more or less equal in the fed state  level in former is about 20 mg%  higher  than later. Even  after accounting for the above mentioned  difference up to 15%  difference  between  capillary whole blood values and laboratory   test acceptable. Thus one need not   doubt reliability of glucometer if he values of laboratory test and glucometer  reading  done  at the same time are not   identical However  glucometer requires periodic cal liberation. This  can  be done every two to three months by simultaneous  testing of blood  glucose  in laboratory  and with glucometer . One should  also remember that Hypo perfusion  and anemia affect capillary  blood glucose Former  give false  low values  while later results  in to false high values. Family physicians  should also   strongly   recommend glucometer   to all the diabetic  patients  for self  monitoring  of blood  glucose.

How & who will train the person or family member if she is too old. Training the patients using glucometer

1)          Frequency of self  monitoring  of blood glucose

The frequency of SMBG depends  on several factors such as sub type of diabetes degree of stability of blood glucose   presence of special situations  In stable and well controlled type 2 diabetes SMBG   is required  once or twice  a week while  in type 1 diabetics  those diabetics  on insulin those with   brittle blood glucose  control and in pregnant   are rough guidelines which will require  modifications in an individual  case

When to test CBG  at domiciliary settings?? Timing of blood  glucose  examination

Routine tests

The timing of blood glucose will depend on individual case.

a)  The usual test timings are pre meals and post meals . Usually initially emphasis is on pre meal monitoring and adjustment of dosages of anti diabetic medications based on pre meal blood glucose values .

b) post meal monitoring Once these are stabilized attention is shifted to post meal monitoring One also has a choice of estimating premeals and post meal values on the same day.

c)  One can plan to test the blood glucose at different times in a rotating manner e.g. on Monday pre breakfast post lunch and post dinner  blood glucose estimation.

d) on insulin therapy :-In addition to pre and post meal estimation occasionally particularly in those  on insulin one should test at 3 am . These values give more precise idea about the level of overnight control and help in taking correct decision regarding adjustment of pre dinner and bedtime insulin dosage. In some patients particularly with relatively  large dose of pre dinner intermediate acting insulin early morning blood glucose dips in hypoglycemic range and reactive hyperglycemia occurs in morning as a result of early morning hypoglycemia. This vicious cycle  can be broken by detecting early morning  hypoglycemia and making appropriate changes in insulin dosage.

f) SOS tests when :

In addition to the test timings mentioned above patients should be advised to do random blood glucose estimation in following circumstances

Q.                       24:-What are the symptoms or signs of hypoglycaemia?? What wrong steps one can adopt during this hypoglycemic attack specially in old women /men who can’t read capillary glucose due to tumbling of their hands or due to poverty not possessing own  glucometer(often the paper strips are exhausted and sons and daughters are abroad). Ans;- What steps are wrongly done more so if a diabetic person resides alone or sleep alone in a winter night ??  Quite often such symptoms are taken lightly and she/ he goes to sleep  again and  die out of H attack. Or another mistake is to consider these as panic/ mania and consider these symptoms of real hypoglycaemia as anxiety related symptoms and don’t take aggressive management. In the process However anxiety related non specific symptoms are also common in the community including in diabetic patients.

Hypoglycaemia if the concerned woman is alone at home but she is educated. In such settings timely SMBG (self monitoring of capillary Glucose can saved her.  Anxious diabetic patients who do not have glucometer or don’t use it during sudden symptom are likely to be caught in a trap if they interpret their anxiety related symptoms as those duet to hypoglycemia and reduce the dose of their anti diabetic medications without consulting their doctor and avoid doing a lab blood glucose test. They also eat snacks very time they get these symptoms disappear on their own however since they have taken a snack they assume that they really had hypoglycemia. These non indicated called for actions lead to hyperglycemia and exposes them to the complications of diabetes.

1)                      The usual symptoms of hypoglycemic attacks are such as hunger, palpitations, sudden sweating.  Giddiness etc. These symptoms could be due to hypoglycemia which needs to be confirmed or ruled out on the spot. Thus timely SMBG (self monitoring of capillary Glucose) =can save precious  time and life as well as lots of money by avoiding delay in hospitalization in case of serious condition such as heart attack or by avoiding  unnecessary hospitalization in cs of simple  hypoglycemic  episode. Prompt   use of glucometer and  SMBG ans swift  appropriate  action  in only one episode will more than  compensate for the entire investment  cost of glucometer.

What is SMBG?? When this type of detailed tets is warranted?? Recording of SMBG data:

It is important to enter each blood  glucose value along with date time and appropriate  comments neatly in tabular form  and take  the data at every consultation visit. This data along with the periodic laboratory blood glucose  tests helps  the treating doctor for fine tuning of anti diabetic medication dosage.  Patients   should be advised to contact you if two   successive readings are out of range so that you can take timely action. This is the precise purpose of doing periodic SMBG (self monitoring of capillary Glucose Those who do not do periodic SMBG(self monitoring of capillary Glucose miss the opportunity to  correct  blood glucose  fluctuations in mid course. Their blood glucose   values remain out of range  till they do laboratory  blood glucose  test. Every day of abnormal blood glucose increases  the chances of developing complications of diabetes

Take home message from Dr S K Pal on DM  who are treated by us

If   family physician can treat and mange DM why not we!!! At all emergency deptt9ER)  the  general duty  medical officer  must have his own  properly cal liberated and functioning  glucometer  all the time with  him in the clinic  as well as on the emergency  visits. He should also encourage self monitoring  of blood glucose by the patients. So also at outré clinic we must have own glucometer & pulse oximtery nowadays.

Are you feeling sleepy after reading these notes. Then omit supper & go to sleep. Send the supper to this old man. Drugs used  in DM

Drug No 1:-Alpha Glucosidase  Inhibitors

Acarbose  miglitol and voglibose are available in India. They act locally on the surface of small  intestine . By inhibiting enzymes which convert complex carbohydrates in to disaccharides they delay   digestion of carbohydrates and convert them in to glucose gradually thus its absorption in   circulation is slowed down and post prandial peaks are blunted. These agents    are not very effective in controlling  fasting blood glucose  and thus are usually used as an adjuvant to other  anti diabetic agents They  tend  to produce  abdominal   distention borbigmy  and diarrhea in many patients  particularly   when given in higher doses  . These  side effects are more common in Indians as   compared with western  people  because   we take a lot of fiber in our diet Usual dose is one  to two  tablets   three  times a day  with meals  the pill to be taken with first bite of food In west many patients  are prescribed  higher dosages but these are not tolerated by Indians.

Indication Of Alpha Glucosidase  Inhibitors

1)          As a monotherapy in patients with mild and predominantly post prandial hyperglycemia if metformin is contra indicated or not tolerated.

2)          As an adjuvant  to insulin metformin glitazones  and insulin  secretogogues for improvement  in post prandial glucose control.

3)          Contraindications

4)          Alpha glucosidase inhibitors are contraindicated in inflammatory bowel disorders  and in pregnancy  and lactation

Precautions

If a patient  develops   hypoglycemia he should be treated by administering glucose  even if hypoglycemia is mild because  in patients on these agents  complex carbohydrates  take longer  time for conversion to glucose

1)          .

Contra indications OF Glitazones:

Glitazones  are contra indicated in hepatic insufficiency and in cardiac failure . they are ineffective in type 1  diabetics . 

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Type 2 drugs:-Incretion Mimetic  and Incretion  Enhancers

Recently two new classes of anti diabetic agents  with novel  and totally  different mechanism of action as compared to insulin and traditional  OADs  have been introduced in clinical  practice Incretion mimetic are  injectable agents while incretion enhances  which  are also known as DPP IV  inhibitors or Gliptin  are oral  agents. Their mechanisms  of action partially  overlap each  other Before   looking in  to these agents  let us review  incretion  physiology

Incretin  physiology

Incretins are hormones secreted by small intestine in response to food intake. The two important  incretins  are GLIP 1, and GIP  . Circulating  levels of these  hormones  particularly    GLP 1 are reduced  in  type 2 diabetics. They respond to iv infusion of GLP 1 but are resistant  to action of GLP Thus it has no therapeutic value.

What is GLP 1?? What is Byetta??    Thus let us now concentrate on GLP  its four important  physiological  actions are :

1)          Glucose  dependant  enhancement of insulin secretion by beta cells.

2)          Glucose   dependant suppression of posts prandial glucagon   secretion by alpha  cells.

3)          Delaying  gastric  emptying

4)          Stimulation of satietary centre in hypothalamus leading  to reduction in appetite.

All these actions lead to control of post prandial blood glucose in normal  persons In type 2  diabetics recued levels of GLP is one of the contributing patho physiological factors  responsible for hyperglycemia GLP 1 has  very short biological  half  life because   immediately  after its  formation and secretion   in ileum, it is  degraded by DPP IV  enzyme  locally secreted  in small intestine. Thus in order to e therapeutically effective it has to be given in continuous iv infusion which is not practicable.

Incretin  emetics

Extenuative which is a synthetic derivative of extending found in saliva of Zila  monster has a biological half life of 2 hours and remains effective for about 12 hours  after sc administration  in human begins. It is available in our country as Byetta since 2007  It  shares all the physiological   actions   of  GLP 1 ad  is not degraded by DPP IV   enzymes. It’s administration in the dosage of 5 to 10 mcg in those   type 2  twice a day 30-60 minutes  before meals  in those type 2  diabetics  with viable  beta cells  leads to significant  reduction  in post  prandial blood  glucose  about 1%  reduction in HbA1c   and some reduction in fasting  plasma  glucose. Its main  advantages over SU are weight  reduction and absence  of  hypoglycemic  episodes  since it acts only in presence  of hyperglycemia. These two properties  have led to its vast popularly in western countries. It is a good alternative to SUs in the management  of type 2 diabetes  particularly  those  who are overweight  and can afford to spend  around 8000 Rs  per month The main  side effects  seen in about 10%   patients are nausea and vomiting starting with  the dose of 5 mcg for four weeks  and then  increasing to 10 mcg if required  helps  to reduce  g I side effects.

Liraglutide : it is a GLP1  agonist having longer  biological  half  life and needs  to be give  once a day  thus  is more patients friendly As compared  to exenatide its other  subtle differences are 1) Less  pronounced effect on gastric emptying leading to lesser reduction of post  prandial blood glucose and also  lesser gastro intestinal side effects 2) It reduces  fasting blood glucose as well as HbA1c  by a greater  extent  , 3) It has  greater  homology  with glucagon like polypeptide 1 . Liraglutide been recently  introduced  in India. Its   dose is 1.2  to 1.8 mg sc once a day. The starting dose is 0.6 mg and if  well tolerated the dose should be stepped up to 1.2 mg after 1 week

What are the indications of Exenatide and liraglutide??? Let’s see what Dr Pal has to say??

Both the agents  are suitable in affording overweight  type 2  diabetics Particularly  if they are not responding to combination therapy  with OADs and they still have some surviving  beta cell mass

Long acting Extenatide : A longer acting version of extenatide with  effective duration  of action up to one week is being developed . In recently  concluded clinical trial  long acting  extenatide  in the dose   of 2 mg sc once  a week has been able   to reduce  HbA1 c by 1.6%  in 20 weeks.

Incretin  enhancers

As mentioned  above  DPP IV is an enzyme secreted by small intestinal mucosa in areas next to incretion  secreting cells . it degrades incretins  including  GLP 1 immediately  after formation  thus making  it ineffective as a therapeutic agent However  now orally active agents  which inhibit DPP IV  enzyme are  available. This action leads to sustained  availability of physiological amounts of incretins  including GLP 1. If given  to diabetic patients these agents  effectively  reduce  blood glucose  level by working through GLP 1.

Sitagliptin is first  agent  from this class which is  available  for day to day practice . It is  given  in once a day in 100 mg  dosage by mouth just before  breakfast it is a bit  less potent than  extenatide because   it does not  have equally potent  actions on gastro intestinal  motility  and satietary centre Unlike  extenatide its use does not lead  to significant  weight  reduction. It is    weight neutral when   used alone  or in combination with  insulin sensitizers  it does not lead to  significant hypoglycemia   because of its  glucose   dependent  action on beta cells. Availability I oral form   is its main  advantage  over extenatide. It  has been in clinical  use for 3 years  while extenatide is in use for  4 years.

It can  be a good alternative for SUs   both as monotherapy if  metformin is unsuitable or in combination  with metformin  and /or  glitazones. In mild renal  impairment the dose  need not be changed. In moderate  and severe renal  impairment  the dose is 50 mg  and 25 mg once a day  respectively Tablets in 50/25 mg strengths are available but the cost of both is same as 100 mg tablets Vildagliptin is another agent  from this class which has been introduced  recently in India. It’s usual dose is 50 mg twice a day  and has  a profile similar to that of  sitagliptin. It is not cleared for use has a profile similar   to that of sitagliptin. It is  not cleared for use in renally  impaired  patients. Both  sitagliptin and vildagliptin are available  in fixed  dose combinations with metormin in our country.

Another  DPPs inhibitor  Saxagliptin  has been  recently  introduced in India. It is  available  as a formulation containing 5 mg tablet  and is administered once daily .

Its indications  and contraindications are same as those of other DPP4  inhibitors.

Linagliptin

In may 20111 a new DPP4  inhibitor 4^th in series linagliptin  was launched in USA, IT has a long  biological half  life as well as  ability to maintain rayed GLP1  level  for about  24 hrs . Thus  it is true once a day agent . It is safe in all grades of renal  insufficiency and is administered in same full therapeutic dose  as in those with normal renal  functions thus frequent   monitoring  of renal functions is not required for those  on linagliptin.

The  main advantages  of extenatide and Gliptins  over SUs are Lack of  weight  gain and hypoglycemic episodes. In addition in  experimental  animals long term  exposure  of these agents has led to some degree  of beta cell preservation Bea cell regeneration replication as well as  reduced  apoptosis have been  postulated SUs do not have  this properly Thus SUs  are expected  to be gradually   replaced by these agents particularly   in rich countries . Due to economic limitations only a small fraction of diabetics   can afford these expensive agents thus  time tested SUs will continue to remain once of the mainstay of oral anti diabetic therapy  in our country   for a long time to come. However  it should be noted that while SUs  have with stood the test of time these new agents are in clinical   use for  very short  time. Thus  it s a bit early to write  obituary of SUs and hail incretion mimetics  and DPPs  inhibitors  as great discoveries  and wonder  drugs. Type 3 Antidiabetic drugs:- OAD ( oral antidiabetic drugs)::_Thiazolidinedione

Glitazones work as insulin sensitizers. Like metformin they act only on peripheral tissues mainly  muscle  and fat cells  and increase their sensitivity to insulin. They do not increase  pancreatic insulin   secretion thus when  given alone or in combination with  metformin  they do not cause  hypoglycemia.

Their action is mediated  through activation of Par gamma activated intra nuclear receptors. The cellular site of action is predominantly adipocyte and muscle cells with some  action on hepatocytes Glitazones sensitize tissues  towards insulin and reduce  circulating  free fatty acid levels.

Rosiglitazone and Pioglitazone  were the two glitazones  available in  our country  till recently  In September 2010 the regulatory authorities of Govt  of India  banned rosiglitazone  following its  ban in advanc3ed countries . Both  have identical  mechanism of action and indications water retention leading  increased volume of fluid  in intra vascular  compartment is liable to occur  with both the  compounds. Precipitation  of incipient   cardiac failure has occurred with both the glitazones thus they  are contraindicated in those in cardiac failure or those who have history  of cardiac failure In addition a meta analysis  published in 2007   associated  rosiglitazone with higher   prevalence of myocardial   infarction and sudden cardiac death Pioglitazone  has a favorable  influence on plasma lipids and was  not associated   with increased prevalence of myocardial infarction or sudden   cardiac   deaths  in any of the clinical   trials  or meta analysis. The usual daily   dose of Pioglitazone is 15  to 45 mg in a single dose. Most of  the Indian authorities do not  prescribe  it beyond 30 mg /day  both  the  agents produce weight   gain  which  can be  as much as ten kegs in some patients.  The weight  gain is mainly due to water  retention  with some contributions from adipogenesiis  and weight  regain due to better metabolic  control . In those with  significant  edema or weight gain glitazones need to be  discontinued.

Does Piogliatzones have any role in modern medicine or it is like a bullock Curt in 2019?? Indications :

2)          In predominantly insulin resistant type 2 diabetic patients Pioglitazone is used as an alternative to metformin particularly if the latter is not tolerated or contra indicated. It can also be combined with metformin when monotherapy with metformin fails to achieve glycemic targets.

3)          In combination with SUs or other insulin secretogogues when latter agents  alone are not sufficient  to control  blood glucose  level.

In triple drug  combination  along with any two from  SU metformin and gliptin group  in  groups when two  drug  therapy  fails to meet  glycemic targets  and the patient  is still some distance  away from end stage  beta cell  failure  . Experienced clinicians can make such a judgment

Uncommon agents: Quick Release  Bromocriptine  Tablets

Conventional  Bromocriptine has been  in clinical  practice  for more  than two decades  for the management  of parkinsonism and Galactorrhoea. Quick release  preparation of Bromocriptine has been introduced  in India  in mid 2010 and in USA in November  2010. It is indicated  in the management   of type 2 diabetes.

In type 2 diabetes dopaminergic tone in hypothalamic area  is reduced . This  is associated  with increased secretion of  noradrenalin in hypothalamic  hypophyseal axis  which in turn leads  to insulin resistance obesity  and hyperglycemia Bromocriptine is dopamine agonist Administration of quick  release version leads to rapid   buildup of its associated  with reduction in insulin  resistance and  improvement  in glycemic status  particularly post  prandial hyperglycemia.

Quick release  bromocriptine has better bio availability  than its  conventional version. It is available  in tablet  form  each tablet contains 0.8 mg of bromocriptine in special quick  release  formulation. The therapeutic   dosage  is 1.6  to 4.8 mg once daily  two hours after  getting  up in morning . preferably  after food. In order to avoid gastro intestinal  side effects treatement  should be started with 0.8 mg and dosage  should  be stepped up at weakly interval.

Quick  release  bromocriptine  is the first and so far only anti  diabetic medication which has successfully undergone  elaborate   pre marketing cardio  vascular safety studies  in USA. After the publication of report    of excess  cardio  vascular  mortality  with  rosiglitazone   in the  New  Engalnd   journal of medicine  in June   2007  Th US FDA has made  these tests  mandatory   for any new  and diabetic  agent  before  its introduction in the market.

Quick release   bromocriptine can be  used as one of the add on agents  particularly  in those  with manifestations of insulin resistance .

Tips from  Dr S K Pal in lieu of a good dinner : It is dinner time for this old man: send your delicious dinner sharp by courier . Clinical  applications of OADs

OADs are indicated in type 2 DM patients  when diet fails to control hyperglycemia. Stressful conditions  such as  severe  infections pregnancy and major  surgery  renal and hepatic  insufficiency are contra indications  to the use  of OADs These  drugs  do not work  in the absence  of insulin hence  should not be  used alone in Type 1 DM.

CRITERIA FOR  CONTORL

 One  should aim at total  freedom form  glycosuria  and steady  near normal blood glucose . Table 2 gives  criteria  for control

Note  : Criteria for control need to be modified as per the individual patient’s  situation

In elderly  people in those  who do not have warning  adrenergic symptoms  and in those with significant cardiovascular  affection with long standing diabetes less stringent criteria should be applied.

During  pregnancy   fasting and 2 hours  post prandial plasma  glucose  values  should be < 100 and 125 mg % respectively . In young  ad recently  diagnosed  diabetic  patients  generally aggressive criteria should be applied. Their  all the three  glycemic values i.e. fasting and post prandial plasma  glucose  values  and HbA1c  should be  at or very   near  lower  limit of the range  mentioned above.

Failure of control

 A common cause  of failure is inadequate   dietary regulations Some diabetes  are under the wrong  impression that since they are taking OAD they are  at liberty to eat anything  . In   addition  to review  of diet in patients   failing to respond  to  OAD a systematic   search for occult  infection   should be made.

It is also  advisable to thoroughly analyze all the medicines  he/ she is taking . In addition to medicines  prescribed by you he/ she  may be taking say for example steroids for asthma  strong  potassium wasting  diuretics like Fursemide  and Diphenythydanatoin  can also interfere with the action of OAD . If a  failure occurs  even after proper  dietary  regulations and maximal  dose of OAD  drugs  from other  groups  should be added and the dosage  gradually  increased  until  optimal  control is  achieved . After  a prolonged use for  several years   OAD  gradually start   losing  their  effect  and  ultimately a stage is reached  in many  patients  where a maximum dosage of combined agents  is also unable  to control  hyperglycemia and  . At this stage OAD should be replaced by insulin.

Side effects

Sulphonylureas : A number  of non specific gastrointestinal  symptoms ranging from dyspepsia to diarrhea occur with the sulphonylura in a small number   of patients  . A  variety of skin reactions also  occur . these are  mostly of minor  significance  and resolve  on drug cessation however  an  occasional   severe complication may arise such as exfoliative dermatitis or stevens Johnson syndrome. A cholestatic  type of jaundice is rarely seen as is bone marrow depression . water  retention   giving rise to delusional Hyponatraemia was  first described  with chlorpropamide  but has also  been reported  with other sulphonylureas Hypoglycemia should be regarded  as a consequence  of excessive  dosage rather  than as a side effect  unless due to drug  interaction

What about Biguanides(metformin- My fair lady!!) : Gastro intestinal side effects including  anorexia nausea and diarrhea occur in 10-15% of patients  and being dose dependent these may limit the opportunity  to employ  maximum dosage. Vitamin B12  deficiency  may result  from the effect of biguanides  on the dowel . In contrast  to the sulphonylureas  hypoglycemia  is rare  and usually is only reported with suicidal drug  use. We have already discussed  lactic acidosis.

What about Glitazones??  : Weight gain  swelling of feet  due to edema and cardiac  failure  when used  in patients  with left  ventricular  dysfunction are main side effects  Mild   anemia is also  seen This is due to dilution of blood following  increased  blood volume due to water  retention.

Alpha  Glucosidase Inhibitors : Abdominal  distention borbigmy  and diarrhea  are main  side effects.

DPPS inhibitors A variety  of skin  reactions are occasionally reported. These are  mostly of minor significance   and resolve  on drug cessation   however   an occasional   severe  complication  such as  exfoliative dermatitis or Stevens johnson  syndrome  has been reported  in those  on sitagliptin Rare  cases of pancreatitis   in those  on sitagliptin   and incretin  mimetics have  been  reported however   cause  and effect has not been proved As such pancreatitis is more    common in diabetics  as compared to others

Incretin mimetics : main side effects are gastro intestinal  intolerance . These can be  reduced by starting the therapy  with smaller dose and subsequently stepping up Pancreatitis has been reported   in rare  cases.

Bromocriptin: Gastro intestinal intolerance is not uncommon The prevalence   and severity is reduced by starting with lower  dose and stepping up after  one week. Giddiness and postural  hypotension  is seen in some patients . Bromocriptine  should be avoided in those  on other  ergot  agents  antipsychotic  agents  and dopamine antagonists.

Drug  Interactions

These  occur mainly with sulphonylureas Alcohol intolerance occurs in a number   of patients  particularly those on chlorpropamide Many drugs  potentiate hypoglycemic   effects of sulphonylureas. These   include clofibrate Dicumarol  large doses of salcylates  Beta  blockers   NSAIDs  and Biguanides In those  taking biguanides  the risk of lactic acidosis increases if they consume alcohol.

 The  entire work was a joint  effort of ADA EASD  IDF and IFCC .

In order in express average blood glucose  in patient  friendly and meaningful manner a large multi centric multinational work was carried out in 700 persons . 300 each had type 1 and 2 diabetes and 100 were normal controls Originally 11  centers  spread across North America Europe Africa  and Asia  were included . One centre dropped out   due to technical reasons.

 Those  having conditions such as anemia haemoglobinopathies and renal impairment  were  excluded from eh study  A large amount   of data on glycemic control was generated in these people by studying  was generated in these  people by studding them for 4 months  in this period   all were subjected

It is proposed that in future IFCC  will standardize and cal liberate    all the equipment used for estimation  of HbA1c  and also officially release the mathematical formula subsequently the laboratories  will give  report in HbA1c    formal  expressed in %  as currently done in mmol/L  format as well as in ear in mg%  format.

In other words HbA1c   will not be done away  with but will  be  standardized and cal liberated by IFCC method  . In addition eAG  in mg% will be calculated by mathematical  formula and given along with HbA1c  report as an additional value 7%  HbA1c  will be equivalent to 154  mg%  of glucose instead of 150mg% as at present . Hence in future indicators of long  term glycemic control and spot  or point of time  glycemic  control will be expressed in same  units. This move will be very much patient  friendly and

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