Diabetes, redefined

New research is changing the way diabetes is being treated

28-Diabetes-redefined

A 30-year-old working woman with no family history of diabetes, a 57-year-old obese man and a 19-year-old lean girl with an unhealthy lifestyle have entirely different physiological and structural makeup. When placed under the scanner for diabetes diagnosis though, they are clubbed together and labelled as type 2 diabetes patients. This is now set to change.

The subgroups, as suggested by the Swedish team, are only applicable to the type 2 population of Scandinavia, not for that of India. —Dr Shashank Joshi, president, Indian Academy of Diabetes
Initially, when shivani Chavan came to us, it was not easy to actually identify which category she would fall in—type 1 or type 2. — Dr Pradeep Gadge, diabetologist, Mumbai
Present classification in type 1 and 2 is quite broad and does not give us complete clarity on the choice of treatment for patients. —Dr Shaival Chandalia, consultant, diabetes and endocrinology, Jaslok hospital, Mumbai
The best thing about the reclassification or subgrouping of type 2 diabetes is that it will help in early diagnosis and focused treatment. — Dr Ramen Goel, bariatric surgeon, Wockhardt Hospital, Mumbai
Until now there are no novel medicines to take care of obesity-related diabetes. Most of the available [medicines] come with side effects. —Dr Mahesh Chikkachannappa, senior consultant, general laparoscopic and bariatric surgery, Aster CMI Hospital, Bengaluru

According to scientists and medical researchers in India, there may be as many as seven subgroups of type 2 diabetes according to which patients can be provided a focused and personalised treatment.

Last March, Swedish professor Leif Groop published his research in The Lancet, suggesting five new subgroups to type 2 diabetes after studying almost 15,000 newly diagnosed diabetics in southern Sweden. He used measurements such as age at diagnosis, body mass index, long-term glycemic control, insulin resistance and presence of auto-antibodies associated with autoimmune diabetes. He claimed that in the case of Europeans, adult-onset diabetes or type 2 diabetes can be further classified into severe autoimmune diabetes (SAID), severe insulin deficient diabetes (SIDD), severe insulin resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). According to researchers and doctors in India who joined the study a few months later, the classification of diabetes stands true for patients in India, too, which reportedly is the diabetes capital of the world with more than 50 million people suffering from type 2 diabetes. “Type 2 diabetes actually consists of several subgroups and we have found that each has significantly different patient characteristics and risk of complications,” says Dr Chittaranjan Yajnik from Pune's KEM hospital who is leading the Swedish project, All New Diabetics in Scania (ANDIS), in India in collaboration with the Swedish Council. “Diagnosis cannot only be based on levels of blood sugar. A number of factors contribute to accuracy in diagnosis and this further classification will help doctors in prescribing accurate and personalised treatment options.”

Experts agree that diabetes is the fastest growing disease worldwide, and as per a report published in The Lancet, the amount of insulin needed to effectively treat type 2 diabetes, in particular, will rise by more than 20 per cent worldwide over the next 12 years. Dr Shaival Chandalia, a consultant in diabetes and endocrinology at Jaslok hospital in Mumbai, says that patients with SIRD or SIDD have the most to gain from the new classification, as they will get precise treatment. “Present classification in type 1 and 2 is quite broad and does not give us complete clarity on the choice of treatment for patients, each of whom has inherent physical, biological and physiological differences,” he says. “Almost 98 per cent of all diabetes cases we see are of type 2 variety.”

The attempt at classification of the disease is not entirely new though. Doctors say that they have always been classifying their patients into varied types, according to cause, duration and prognosis, but only in their heads. “Until now, we mostly used our intuition to treat type 2 patients,” says Chandalia. “For example, if somebody is overweight, her insulin resistance must be high. A tablet such as metformin or pioglitazone will help in reducing the resistance. That is how we have been working. But with developing research, scientists are laying stress on going to the root to understand the type of pathophysiology that is responsible for the particular type of diabetes so that we can determine the cause of the disease as well as the type of medication to be used.”

Shivani Chavan Shivani Chavan

The ANDIS project classification, however, is a European classification for Scandinavians and Caucasians. Dr Shashank Joshi, president of Indian Academy of Diabetes, says an Asian diabetic is different from a Caucasian one. “The Asian phenotype of type 2 diabetes is quite distinct,” he says. Type 2 diabetes in India, says Joshi, is hotchpotch and heterogenous and the most complicated of all, whereas in Europe it is quite homogenous. “We, in India, see type 2 in thin people, those with normal BMI range but abdominal fat, and also among overweight and obese people,” he says. “And, the subgroups, as suggested by the Swedish team, are only applicable to the type 2 population of Scandinavia, not for that of India. We need to do our own stratified sampling of our phenotype and Yajnik is certainly not doing that.” He explains that in India there are more than 10-12 variants of type 2 diabetes, with two major peaks, one that comes during adolescence and the other that comes in later life. Also, type 2 diabetes varies with topography. “We have state-specific diabetes, too, such as Kerala diabetes and Odisha diabetes, both mostly due to malnutrition. There is MODY (maturity onset diabetes of the young), too. So, with such heterogeneity, it is not possible to classify type 2 into five subgroups only.”

According to a 2009 study, among 16,000 patients from eight regions of Maharashtra, type 2 diabetes came with problems of hypertension and lipid profile abnormality, and the common thread between all of them was the abdominal circumference. Joshi explains that if one's waist circumference is more than 90cm in men and 80cm in women, it can lead to the twin problem of blood pressure and diabetes. “It is a triad of blood pressure, diabetes and cholesterol coming together,” he says.

Nonetheless, the five subgroups are a starting point in understanding and managing type 2 diabetes better.

SEVERE AUTOIMMUNE DIABETES
This type essentially corresponds to type 1 diabetes and LADA (latent autoimmune diabetes in adults), and is characterised by onset at young age, poor metabolic control, impaired insulin production and the presence of glutamic acid decarboxylase antibodies (GADA). A year ago, 17-year-old Shivani Chavan was diagnosed with juvenile diabetes—a chronic condition in which the pancreas produces little or no insulin. A random blood test revealed that her sugar level had shot up to 490mg/dL. Normal sugar levels range between 85mg/dL and 120mg/dL. She was then prescribed a high dose of insulin—about 40 units of Actrapid and Lantus—which she continues to take five times every day without fail. “It was quite difficult initially to prick myself so many times. And, I have to strictly abide by the timings because otherwise the sugar levels would spike and I would feel dizzy and low,” says the resident of Bhayander, a Mumbai suburb.

Dr Shaival Chandalia Dr Shaival Chandalia

Chavan, a mechanical engineering student, gained weight—from 57kg to 64kg—within six months of taking insulin. The initial months were too much to take, says Chavan, who ended up on the college's defaulters' list because of the many leaves she took for undergoing a battery of tests. But now she is used to her condition. Her sugar levels are under control, she says, thanks to diet and exercise. “It is below 200 now and my HbA1c (haemoglobin A1c) is 8.9 at present, while upon diagnosis it was 13,” says Chavan, who is now busy prepping for her exams. To keep her sugar levels under check, she will have to take insulin all her life.

“Initially, when Chavan came to us, it was not easy to actually identify which category she would fall in—type 1 or type 2. When such patients who are in their teens and are obese or overweight come to us, we get into a dilemma because they can fall into either categories,” says Dr Pradeep Gadge, a diabetologist in Mumbai. Type 1 diabetes is where the patient must be put on a lifetime of insulin as the production of insulin in the body stops, while type 2 diabetes is more related to lifestyle habits and genetics. “Upon conducting the GAD antibody test, indicating autoimmunity, which came back positive, we could figure that she was a type 1 diabetic. So, there was no point in trying to give her oral medications because such patients require insulin only,” says Gadge. “So, the sub-classification that the ANDIS project seeks to do will help practitioners like me in deciding the line of treatment, not experimenting with oral medications where they would not work, identifying the autoimmunity early on and in establishing the long-term prognosis of the treatment.”

MILD OBESITY-RELATED DIABETES

This subtype includes obese patients who fall ill at a relatively young age. “Most people who are obese eventually develop diabetes because the body can produce only that much of insulin for an ideal body weight,” says Dr Mahesh Chikkachannappa, senior consultant, general laparoscopic and bariatric surgery, Aster CMI Hospital, Bengaluru. “And nowadays because of the lifestyle we lead, this particular subtype may be more common among the middle age group. In turn, it is also true that diabetes leads to obesity because of decrease in metabolism and storage of fat and cholesterol in the body. Roughly, I would say about 60 to 65 per cent of obese people in India have diabetes and hyper cholesterol and blood pressure issues.”

Dr Ramen Goel Dr Ramen Goel

When Chitra Mane (name changed on request), 38, visited Aster hospital, she weighed 110kg with a BMI of 43. A BMI reading between 19 and 25 is considered to be an indicator of healthy body weight, while a BMI reading above 30 indicates obesity. She had been overweight since her teenage years and post two pregnancies, she gained even more. “She found it very difficult to lose weight and whatever she lost would bounce back quickly. The excess weight led to obesity and a nagging pain in the knees and the back,” says Chikkachannappa.

He, along with his team of doctors, suggested that Mane undergo a sleeve gastrectomy—a keyhole bariatric surgery in which the stomach is reduced to a fraction of its original size by surgical removal of excess portion. Five months post the surgery, she lost 35kg, “felt lighter and better” and has stopped taking medicines to control her blood sugar because now the body does not need high dosage to keep the insulin level in check. “Mostly we bracket obese or overweight diabetics under the type 2 bracket, which is quite a heterogenous group. These patients start with oral medications and then eventually move on to insulin. But if uncontrolled diabetes persists and BMI goes above 34, we advise bariatric surgery,” says Chikkachannappa.

A classification of type 2 diabetes into a class of diabetes that is more prone to obesity will help in prescribing focused treatment, says Chikkachannappa, which will at most times be bariatric surgery. “But that is also because until now there are no novel medicines or tablets to take care of obesity-related diabetes,” he says. “Most of the available [medicines] come with side effects.”

Agrees Dr Ramen Goel, a bariatric surgeon at Wockhardt Hospital, Mumbai: “Patients who have insulin resistant diabetes are generally good candidates for bariatric surgery because this surgery reduces insulin resistance immediately after surgery to the extent of 90 per cent. So, depending on the case, these subgroups also kind of overlap.”

He cites the example of Priti Shardul, 65, who was first diagnosed with diabetes at 40. She initially took Glycomet 500mg twice a day, but switched to insulin eight years ago because of increased weight. Last year, she underwent bariatric surgery when she was a little short of 100kg. “I would fall down frequently as my legs would not be able to take the weight of my body. My blood sugar level went over 250mg/dL and I was on 70 units of insulin every day,” says Shardul. Today, she is slimmer by 30kg.

“The best thing about the reclassification or subgrouping of type 2 diabetes is that it will help in early diagnosis and focused treatment,” says Goel. “For example, in the case of Shardul, had we known at the start that her diabetes had a predisposition towards obesity, the treatment would have been prescribed accordingly.”

MILD AGE-RELATED DIABETES

This subtype covers a large part of India's population, in which many elderly patients suffer from diabetes. Dr Sonal Dalal, nephrologist from Ahmedabad's Sterling Hospital, cites the example of a 65-year-old patient who has been under her care for seven years. “He will soon undergo dialysis because his kidney function has reduced to less than 15 per cent,” she says. “The primary cause, of course, has been MODY diabetes, which is essentially age-related. He never opted for regular checkups and was caught unawares when his creatinine had shot up to 1.6mg/dL. Since the past few months, his creatinine is around 7mg/dL.” Normal creatinine levels range from 0.6mg/dL to 1.2mg/dL. Early identification of a subtype of diabetes prone to kidney damage will help in giving timely treatment and, in the best case scenario, prolong dialysis by five to seven years, says Dalal. “Also, we can provide patients with renal protective drugs if we know well in advance that her type of diabetes is prone to renal damage,” she says.

Dr Mahesh Chikkachannappa Dr Mahesh Chikkachannappa

Diabetic kidney disease, says Dalal, is reversible only in very early stages. Once the creatinine levels start moving up, it becomes difficult to bring the disease under control. O.N. Boni, 79, suffers from type 2 diabetes that has severely impacted the function of his kidneys. He might have to undergo dialysis next month, but Boni, who was diagnosed with diabetes at 45, hopes he can delay it with his dietary precautions and daily strolls. His breakfast is usually rice bhakri and meals that consist of boiled vegetables. “I have also considerably reduced my salt intake and I keep my sugar levels under check,” he says.

Knowing that a certain type of diabetes is prone to kidney damage, it is possible to delay the progression of the kidney disease even if one cannot entirely stop it. Dalal says a patient's sugar levels, HbA1c and microalbumin levels must be checked every six months. Albumin (blood protein) in the urine is one of the first proteins to leak when kidneys get damaged.

SEVERE INSULIN-DEFICIENT DIABETES AND SEVERE INSULIN-RESISTANT DIABETES

SIDD is characterised by high HbA1c, impaired insulin secretion and moderate insulin resistance, say doctors. “A patient with severe insulin deficiency would be someone whose pancreatic beta cells are not performing at all. This means that no oral tablets will work because most of them work primarily through the pancreas. Hence, these people will most likely require insulin sooner rather than later,” says Dr Sandeep Gulati, a Delhi-based nephrologist.

Even someone who falls in the category of type 1 juvenile diabetes can be classified under SIDD because she will require insulin for survival, says Gulati. “But even those who have been type 2 diabetics for about 15 to 20 years, who were on tablets earlier but have moved on to insulin, fit the definition of SIDD,” he says.

As against this, SIRD is characterised by obesity and severe insulin resistance. It is also said to be the group with a very high incidence of kidney damage. “Here we have patients who weigh 120kg to 150kg and their insulin requirement is very high. It can go up to 100 to 200 units per day and even in countries like the US the insulin requirement can go up to 500 units per day,” says Dr Ashutosh Goyal, senior consultant, department of endocrinology and diabetes, Paras hospitals, Gurugram. The high insulin requirement, says Goyal, is because such patients are more obese and are less physically active, so insulin resistance is more in them. “So, we need to administer high doses of insulin externally. If a patient requires more than two units of insulin per kilo of body weight per day... then it is a case of SIRD,” he says. While such patients have always been there, says Goyal, classifying them into a focus category is new and welcome, too. “This classification will be helpful in the future,” he says, “as it will enable us to determine the exact course of action or give precise medicine as per the condition.”

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