Dr. V Mohan, as part of this exclusive 12-article series on Diabetes, answers questions posted by readers on a previous article of his- Treatment algorithm; factors to consider while prescribing medication.

Question 1: Is there any clinical investigation which can differentiate clearly between various types of type 2 diabetes so that treatment can be done accordingly?

Dr. V Mohan: In the new subtypes of diabetes proposed by Leif Groop and colleagues from Scandinavia, 5 major types of type 2 diabetes are described*.

1. The first one which is severe autoimmune diabetes is what was previously called as Latent Autoimmune Diabetes of Adults (LADA). These patients tend to be thin. Their insulin secretion is low and hence C-peptide levels would be low and the GAD antibodies are positive.
2. In the second type called severe insulin-deficient diabetes, C-peptide levels will be low, but they may not have signs of insulin resistance like acanthosis nigricans, obesity etc.
3. The third type is called severe insulin resistant diabetes or SIRD. These patients have marked obesity and signs of insulin resistance and also metabolic syndrome with raised triglycerides, low HDL, hypertension and central body obesity in addition to the diabetes, and hence we can easily distinguish them clinically. These are the typical obese, diabetic patients that we often see in our practice.
4. The fourth variety of type 2 diabetes is called as Mild obesity-related diabetes or MOD. Here the obesity is not very marked and there is no evidence of metabolic syndrome. So their waist circumference may not be increased but their BMI may be just above normal.
5. Finally, we have the age-related variety of type 2 diabetes, where the diabetes sets in after 60 or 70 years of age. The diabetes in these patients normally tends to be mild.

So using our clinical judgement, along with a proper clinical examination to look for evidence of acanthosis nigricans, measurement of waist circumference, and where facilities are available- C-peptide or GAD estimations, we should be able to classify the majority of these forms of diabetes.

They also have prognostic implications. For eg: the third variety, ie. The patients with the Severe Insulin Resistant Diabetes (SIRD) are more prone to diabetic kidney disease and to fatty liver. On the other hand the Severe Insulin Deficient Diabetes (SIDD), patients are more prone to retinopathy and neuropathy. Hence it is useful to have these classifications.

*Source: E Ahlqvist et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. The Lancet Diabetes and Endocrinology. Volume 6, ISSUE 5, P361-369, May 01, 2018. DOI: https://doi.org/10.1016/S2213-8587(18)30051-2

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Question 2: If the patient is a obese 50-year-old with border-line sugar- what should be the line of treatment? Should the patient be considered for MOD ?

Dr. V Mohan: If the patient is grossly obese, then he would come under the severe insulin resistant form or SIRD variety, whereas if the obesity is mild and there is no metabolic syndrome the patient would come under mild obesity-related diabetes or MOD. If it is an older patient above 60 or 70 years of age, he or she will come under the mild age-related diabetes or MARD.

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Question 3: How can we treat newly detected DM? Is there is any algorithm?

Dr. V Mohan: There is no one treatment for all patients with newly-detected diabetes.

1. We can have a patient who is newly detected but only has an HbA1c of 7.5%. This patient would respond to diet and exercise along with metformin.
2. On the other hand we can have a newly detected patient who has an HbA1c of 12.5% and may be symptomatic with weight loss and evidence of glucotoxicity. These patients are best treated with a short course of insulin for almost a month along with a combination of oral drugs and diet and exercise, as they do really well because the insulin helps to correct the glucotoxicity.

So depending on the clinical presentation we can plan the treatment for new patients accordingly.

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Question 4: One of the biggest problems is dealing with pain, either musculoskeletal, arthritic, or neuropathic. Please elaborate on how to deal with it.

Dr. V Mohan: Body pain is very common in people with diabetes. However, those who do regular exercise and do stretching exercises or yoga very rarely have such pains. If there is arthritis, we have to find out which type of arthritis they have and treat them accordingly.

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Question 5: Is it advisable to use Sitagliptin along with Metformin (50/1000) twice a day for Type 2 DM? Is there risk of Pancreatitis?

Dr. V Mohan: The risk of pancreatitis with the Sitagliptin and other DPP4 inhibitors is very very low. You should remember that all patients with diabetes have an increased risk of having pancreatitis. It is true that the DPP4 inhibitors as well as the GLP1 receptor do lead to a very slight increase in pancreatitis, but in my practice, I have not seen this to be a cause for concern. Of course, if somebody already has a history of pancreatitis, then it is better to avoid this group of drugs.

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Question 6: How to confirm SIDD and to differentiate it from SAID?

Dr. V Mohan: In SAID, there is evidence of autoimmunity and hence GAD antibodies or Zinc transport antibodies or IA2 antibodies may be positive. SAID is nothing but what was earlier called as Latent Autoimmune Diabetes of Adults (LADA) and it is a variant of type1 diabetes.

SIDD on the other hand is type 2 Diabetes where the insulin deficiency is the major defect. They tend to have low C-peptide levels and they are thin and do not have evidence of insulin resistance or obesity. Clinically it is very difficult to distinguish SIDD from SAID, but doing GAD antibody test is useful to cinch the diagnosis

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Question 7: After diagnosis of diabetes, how to proceed for further identifyication of type of diabetes- whether type 1, type 2 or monogenic form? Please elaborate.

Dr. V Mohan: There are clinical criteria which one can use.

1. If it is patient of a younger age group who has an abrupt onset of diabetes, with no family history, and if they are thin, have low c-peptide and if the GAD antibodies are positive, then the diagnosis of type1 diabetes is pretty obvious.
2. If the patient is older, has a strong family history, is obese and has an insidious onset, it is most likely type 2 diabetes.
3. In monogenic diabetes, patients normally have 3 generation transmission of diabetes in the family. They are lean like the type1 diabetic patients but GAD antibodies are negative.
4. A diagnosis of MODY or Monogenic Form of diabetes can be done only after doing genetic testing and this can be done if the clinical picture strongly suggests it.

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Question 8: Please provide information about reference articles for subtypes of type 2 Diabetes Mellitus.

Dr. V Mohan: This subtypes of type 2 diabetes was described by Leif Groop and colleagues from Sweden and the reference for this is the paper titled Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables by Ahlqvist et al in The Lancet Diabetes & Endocrinology (check for link above in Answer 1).

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Question 9: Can diagnosis of type 2 DM be done depending on random blood sugar?

Dr. V Mohan: If the random blood sugar is more than 200 mg on more than 2 occasions, then one does have diabetes. The other diagnostic criteria for diabetes is a 2-hour value more than 200 in GTT, fasting more than 126, or a HbA1c more than 6.5%. All these will only tell you whether diabetes is present or not. To diagnose type 2 diabetes, you have to look for the clinical features of type 2 diabetes.

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Question 10: What about treating a 80-year-old diabetic on drugs? What is fasting and postprandial blood sugar for them?

Dr. V Mohan: In people who are 80 years old, obviously we should not be very aggressive in the treatment, and importantly we should avoid hypoglycaemia as much as possible. There is no fixed target, but certainly we need not aim for HbA1c targets of below 7. We can relax it and HbA1c of up to 7.5 or 8% may be okay for these individuals. Similarly, we can relax the fasting and postprandial blood sugar targets also.

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Question 11: What is your opinion/experience regarding herbals in the management of type 2 DM. It seems like many type 2 DM patients keep their DM well under control.

Dr. V Mohan: I do not have enough experience with herbal treatment as I am an allopathic doctor. However, I have done clinical trials on several Ayurvedic compounds. They do have some effect, but they are mild and usually more beneficial in the early stages of diabetes.

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Question 12: Should we start treatment for pre-diabetic patients or should one solely advice and rely on the patient's lifestyle changes?

Dr. V Mohan: The best treatment for people with pre-diabetes is lifestyle modification. However, there are some patients who have a strong family history of diabetes, obesity, and tendency for rapid progression. In such people, metformin can also be used. Frequent follow up is also needed.

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Question 13: Can treatment given for cancer initiate diabetes in the patient?

Dr. V Mohan: Yes, indeed there is a link between cancer treatment and diabetes. Several drugs used for cancer can precipitate diabetes including steroids and many of the chemotherapy drugs.

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To read articles published in the series, click,

Treatment algorithm; factors to consider while prescribing medication: Dr. V Mohan

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This article was originally published on November 5, 2019.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. V Mohan is the Chairman & Chief of Diabetology at Dr. Mohan’s Diabetes Specialities Centre & Madras Diabetes Research Foundation, Chennai, India.