# RKS: OBESE DIABETIC? - Dieting vs Pills

 

# RKS: OBESE DIABETIC?

- DIETING vs PILLS

1st January 2023

KETO DIET FOR T2DM

A WORTHWHILE CONSIDERATION OR A STRICT NO-NO?

Dear Reader,

The world has 13% prevalence of obesity - 1 billion (bn) of population, in addition to another 1 bn being overweight. Except for Madagascar, Eritrea and Ethiopia the balance 192 countries of the world has obese population and hence the malady is truly termed as 'globesity'. 

The Pacific islands are the leaders in the globesity epidemic since, unlike any other country, more than 50% of their population is obese. [https://worldpopulationreview.com/country-rankings/obesity-rates-by-country]

1. Nauru: 61%
2. Cook Islands: 56%
3. Palau: 55%
4. Marshall Islands: 53%
5. Tuvalu (Ellis Islands): 52%

Vietnam has the least prevalence and only 2.1% of its population is obese. Obesity is estimated by calculating the Body Mass Index (BMI) and depending upon its values, the overweight are differently classified as obese.

Type 2 diabetes mellitus (T2DM) is the leading cause of Years Lived with Disability (YLD) related to BMI, followed by disorders of muscles and bones and then heart disease. [NEJM 2017; 377(1): 3-27] 60-90% of diabetics suffering from T2DM are obese. In India, the prevalence of generalized obesity (GO), abdominal obesity (AO), and combined obesity (CO) amongst diabetics is 58.68%, 81.84% and 53.42%, respectively. [Ind J Health Sci and Biomedical Res KLEU 2020; 13(1): 21-27]

If the obesity is not tackled in T2DM, the individual diabetic could have very much enhanced risks of complications such as: [Global Burden of Diabetes: Part 1. In: Global Report on Diabetes. World Health Organization. WHO Press (Switzerland) 2016; pp 20-33]

• Heart disease: 2-3 times more chances in diabetics, but obesity per se can increase suffering from coronary diseases by 28%. [O'Hare R 2017; https://www.imperial.ac.uk/news/181111/fat-increased-risk-heart-disease/]
• Loss of vision (proliferative retinopathy): 7% incidence in diabetics but obesity could facilitate its worsening.
• Kidney failure (nephropathy): 10 times higher risk in diabetics and 2-3 fold enhanced nephropathy incidence reported due to obesity per se. [J Am Soc Nephrology (JASN) 2006; 17(6): 1695-1702]
• Leg amputation: 10-20 times greater possibility.
• Nerve damage (neuropathy): 12% prevalence due to obesity in non-diabetics vs 41% in obese diabetics. [Mayo Clin Proc 2020; 95(7): 1342-1353]
• Paralysis (due to stroke): 5% increase in stroke risk with every 1 unit increase in BMI. [Stroke 2013; 44: 278-286]

Thus, it is implied that reducing weight is an important goal especially if the bite of diabetes is to be blunted.

HOW TO REDUCE WEIGHT IN DIABETICS?

It has always been a pipe-dream to reduce weight for a diabetic. Notwithstanding the seriousness of the complications there is invariably never a persistent, serious effort nor a result-oriented full-proof available option for escaping the obesity trap of T2DM.

Either the diabetic is mentally resigned to the fate of suffering from its known complications since he / she is too well familiar with - having seen how family, relatives or friends have already been inflicted with these, or he / she runs helter-skelter to remedy his / her obesity believing that by so-doing he / she is assured of lessened YLD - which is otherwise a curse of T2DM. 

PILLS FOR WEIGHT LOSS

There are no safe drugs till date available which could address the obesity with an iron hand. However, the current options include:

• Orlistat: Widely known as Xenical (by Roche), orlistat is available in India under plentiful of different brand names. Although it works attractively by decreasing absorption of one-third of fats consumed in food, the drug has never been popular due to its side effects like abdominal cramping, passing gas, leaking oily stool, instigating more bowel movements, and not being able to control feces evacuation. Orlistat could even interfere with absorption of certain vitamins like A, D, E and K - and the same need to be separately supplemented 2 hours before / after ingesting the drug.

• Naltrexone and Bupropion combo: Available as Contrave by Takeda, naltrexone is approved to manage alcohol and opioid dependence whilst the bupropion component is approved to treat depression, seasonal affective disorder, and to help stop smoking. The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia and dry mouth. Additionally, the combination of naltrexone and bupropion can increase risk of suicidal thoughts and behavior, besides its potential raise blood pressure and heart rate.

• Phentermine and Topiramate combo: Qsymia launched by Vivus in US is a very promising combination of phentermine which curbs appetite and topiramate, an anti-migraine and anti-epileptic drug. Topiramate causes weight loss in several ways, including helping one feel full, making foods tasteless, and burning more calories. The most common side effects of Qysmia are tingling hands and feet, dizziness, altered sense of taste, insomnia, constipation and dry mouth. One should avoid taking this combination of agents if suffering from glaucoma, heart disease or stroke, or having high thyroid hormone levels.

Orlistat usage is besieged with problems of compliance because of its 'farting-causing' side effect. In the case of naltrexone + bupropion if the combo does not cause 5% loss of weight in 12 weeks the consulting doctor could stop since the product is known to be not useful for every individual consuming it. Ditto for phentermine + topiramate duo but for this combination if the weight loss recoded is less than 3% in 12 weeks, the same could be continued by the treating doctor with an increase in the dose.

If there is obesity + diabetes, then specific anti-diabetic drugs could be preferred which have additional potential to cause weight loss, besides controlling the blood sugar levels per se. The currently available ones include:

• Liraglutide / Terzepatide / Semaglutide: These anti-diabetics belong to a new class of drugs called Glucagon-like Peptide-(GLP)-1 Agonists. GLP-1 agonists need to be injected weekly beneath the skin (subcutaneous), just like insulin injection, and these agents reduce weight by telling the brain (like naturally secreted intestinal hormone, GLP-1) that the stomach is full and resulting in cutting down of further intake of calories as food. All GLP-1 stimulating drugs can precipitate nausea, vomiting, diarrhea, constipation and lower blood pressure; liraglutide, in particular,                                                                                            has also been reported to cause serious side effects which include raised heart rate, inflammation of pancreas, gallbladder disease, kidney problems, suicidal thoughts and even tumors.

• Metformin: This well-known drug preferred as first-line for obese diabetics actually causes insignificant weight loss - 29% of T2DM overweight patients have been reported to lose 5% or more of their body weight, and just 8% loose around 10%.

Doctors tend to discontinue GLP-1 analogues if weight loss is not as per expectation in the time-frame specified; also many of these agents have yet to get a nod from authorities for use as weight-loss advantage in diabetics. Discontinuing semaglutide and others can result in quick regain of the lost weight. Overall results with metformin have been disappointing, and for weight loss, minimum 2 grams (gm) dose per day is required.

METABOLIC SURGERY

Bariatric surgery refers to any surgery for weight-loss in which changes are made in the digestive system to help shed off excess kilos. To reduce the complications of diabetics with concomitant obesity, the bariatric surgery needed and performed in many is also called as 'metabolic surgery'. 

The American Society for Metabolic and Bariatric Surgery (ASMBS) as well as the American Diabetes Association (ADA), and endorsed by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), recommend bariatric surgery for the following classes of obesity.

• SEVERE OBESITY: Irrespective of diabetes control.
• MODERATE OBESITY: When blood glucose is inadequately controlled despite lifestyle changes and optimal medication.
• MILD OBESITY: If the control of sugar levels in T2DM is unsatisfactory inspite of even adding injectable medication. 

There has been a reported decline in neuropathy, retinopathy and nephropathy, on account of bariatric surgery for obese diabetics, by 17-35% at the end of 5 years post-operation. Even the risk of heart attack drops by 50-60% on account of metabolic surgery performed in suitable cases of T2DM. [Type 2 Diabetes & Metabolic Surgery. Fact Sheet: American Society for Metabolic and Bariatric Surgery (ASMBS); https://asmbs.org/resources/type-2-diabetes-and-metabolic-surgery-fact-sheet]

DIETING

The best 3 diet plans as of 2022 rated are: [Cohen M. 11 Best Diets for Weight Loss in 2022, According to Experts. https://www.prevention.com/weight-loss/diets/g29462611/best-diets-weight-loss/]

1. Mediterranean Diet: Based on the heart-healthy lifestyle of Greece, Italy, Spain and Portugal, the Mediterranean-style diet includes healthy fats such as avocados, olive oil, nuts, plenty of beans, fruit, leafy greens, whole grains and even a daily glass of red wine -  plus, at least twice a week, fish.
2. DASH Diet: The low-sodium Dietary Approaches to Stop Hypertension (DASH) Diet was designed as a way to help people control their blood pressure without using drugs. DASH emphasizes on consuming fruits, vegetables, whole grains and low-fat or non-fat dairy with limiting of saturated fat and dietary cholesterol.
3. Flexitarian Diet: The Flexitarian Diet is a style of eating that encourages eating mostly plant-based foods while allowing meat and other animal products in moderation - combination of vegetarianism + flexibility. The diet entails consuming mostly fruits, vegetables, legumes and whole grains, besides curtailing added sugar and sweets, AND permitting meat and animal products from time-to-time.

Mediterranean diet can reduce weight loss by 10 kgs (22 lbs) in one year whilst DASH dieters will loose 1.4 kgs (3.1 lbs) over 8-24 weeks. Flexitarian diet, as compared to non-vegetarians, ensures lower BMI - but strict vegetarians have least BMI values. Basically, Flexitarian diet is not aimed for weight reduction, it is only to ensure healthy living. 

Popular diets simply don’t work for the vast majority of people. Or more accurately, they are modestly effective for a while, but after a year or so the benefits are largely gone and 97% regain their lost weight! 

KETO DIET

In a large systematic review and meta-analysis, recently published in The British Medical Journal (BMJ), researchers analyzed 121 trials that enrolled nearly 22,000 overweight or obese adults who followed one of the 14 popular diets, including the Atkins, Weight Watchers, Jenny Craig, DASH and the Mediterranean diet, for an average of six months. The diets were grouped into one of three categories: low-carbohydrate (carb), low-fat and moderate-macronutrient (diets in this group were similar to those in the low-fat group, but with slightly more fat and slightly less carb). Both the low-carb and low-fat diets resulted in weight loss of about 4.5 kgs [10 pounds (lbs)] after six months. [Shmerling RH. When Dieting Doesn't Work. Harvard Health Publishing. https://www.health.harvard.edu/blog/when-dieting-doesnt-work-2020052519889]

To realize the benefits of dieting, the real challenges are commitment and patience, according to scientists at the National Institutes of Health (US). Medically, the weight loss achieved is considered significant if at least 5% of body weight is reduced over 6-12 months. An average Indian weighs 65 kgs and has a height of 174 cms (1.74 m); an obese individual weighing 76 kg (BMI=25) – 91 kgs (BMI=30) has to loose 11-26 kgs which could take 1.5 to 2.5 years at the rate of 5% weight loss per every 6 months if the normal BMI target of <23 kg/m2 is to be attained. To wait for over an year to even 5 years for achieving the desirable weight loss with persistent dieting is definitely defying will-power to refrain from eating the cherished foods.

As against the modest weight loss achievable with the otherwise popular diets, pursuing Keto diet can result in 2.3 kgs (5 lbs) in one week; 4.5 kgs (10 lbs) in one month; and even a dramatic 11.3 kgs (25 lbs) in 3 months! Such marked reduction in weight loss is very attractive for all those fanatics whose aim is to shed flab sans indulging in long-term efforts in terms of physical activity maintenance, and need for a sustained will-power for prolonged periods to persist with dietary restrictions. 

WHAT IS A KETO DIET?

The ketogenic or “Keto” diet is a low-carbohydrate (carb), fat-rich eating plan that has been used for centuries to treat specific medical conditions. This diet is gaining considerable attention as a potential weight-loss strategy due to the low-carb diet craze, which started in the 1970s with the Atkins diet (a very low-carbohydrate, high-protein diet, which was a commercial success and popularized low-carb diets to a new level). 

Many other low-carb diets including the Paleo, South Beach and Dukan are all high in protein but moderate in fat. In contrast, the Keto diet is distinctive for its exceptionally high-fat content, typically 70% to 80%, though with only a moderate 10-20% intake of protein and 5-10% carbs. 

KETO DIET FOR OBESE T2DM INDIVIDUAL

Fasting and other dietary regimens have been used to treat epilepsy since at least 500 BC. To mimic the metabolism of fasting, the Ketogenic Diet (KD) therapy was introduced by modern physicians as a treatment for epilepsy in the 1920s. KD has also been tested and used in closely monitored settings for cancer, polycystic ovary syndrome, Alzheimer’s disease besides T2DM. One can experiment with Keto dieting if suffering from T2DM, but KD therapy is to be strictly avoided for reducing weight if diabetes is of juvenile / T1DM (type 1 diabetes mellitus) variety.  

If a T2DM sufferer chooses to start a KD, it is recommended to consult with one’s physician to closely monitor any biochemical changes after starting the regimen, and a dietitian to create a meal plan that is tailored to one’s existing health conditions as well as to prevent nutritional deficiencies or other health complications. A dietitian may also provide guidance on reintroducing carbohydrates once weight loss is achieved. If one desires a more accurate assessment of successful ketosis achieving, ketone levels in blood, urine or breath could be monitored every week. For an easy assessment of ketosis induced by KD, dipsticks for urine ketones estimation are available but these cannot detect mild rise in ketone bodies - blood meter is the gold standard in ketone measurement.

Ketoacidosis, the most dreaded complication of KD therapy, is a possibility in T1DM but has not been a reported concern in those with obesity-associated T2DM.

SUMMARIZING

Intentional weight loss in obese individuals appears to have a beneficial effect on mortality risk for those having T2DM disease. In thousands of obese diabetics evaluated between 1966 and 2001 a 25% weight loss was reported to reduce mortality risks by 25%, besides improving metabolic handling of glucose by 80%! A weight loss of 9-13 kg has been documented as the most protective, and hence best desirable for favorable outcomes in those obese. [Diabetes Obes Metab 2004; 6(2): 85-94]

In a 2012 study of all cardiometabolic deaths (heart disease, stroke and T2DM) an estimated 45.4% were associated with non-optimal intakes of 10 dietary factors. The largest estimated mortality was associated with high sodium intake (9.5%), followed by low intake of nuts and seeds (8.5%), high intake of processed meats (8.2%), low intake of omega-3 fats (7.8%), low intake of vegetables 7.6%), low intake of fruits (7.5%), and high intake of artificially sweetened beverages (7.4%). The lowest estimated mortality was associated with low polyunsaturated fats (2.3%) and unprocessed red meats (0.4%). [Masood W, Annamaraju P & Uppaluri KR. Ketogenic Diet. (Updated 2022 Jun 11). In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2022 Jan-] Hence, a Keto diet that advocates low consumption of carbs, more of saturated fats (which includes meat products) cannot be a concern for health and healthy living. 

In a meta-analysis study including 13 trials and 567 patients of T2DM the following were the outcomes of Keto diet recorded. [Nutr Diab 2020; 10: Article 38;  https://doi.org/10.1038/s41387-020-00142-z]

1. Diminished insulin resistance: The calculation is based on Homeostasis MOdel Assessment of Insulin Resistance (HOMA-IR) which is derived by: (fasting serum insulin (μU/ml) × fasting plasma glucose (mmol l-1)/22.5). Optimal insulin sensitivity is indicated if HOMA-IR is less than 1; levels above 1.9 signal early insulin resistance; and values more than 2.9 denote significant insulin resistance. Usually diabetics have HOMA-IR values ranging from  1.6 to 7.2 and Keto diet can cause a decline of HOMA-IR by 3.4 in those with T2DM and having a BMI of more than 30 kg/m2. [BMC Endocrine Disord 2013; 13: Article 47; https://doi.org/10.1186/1472-6823-13-47; Exp Therap Med 2022; 23(1): Article 73; https://doi.org/10.3892/etm.2021.10996]
2. Lessened HbA1c (Glycated Hemoglobin): Keto diet can reduce HbA1c by even upto 1.5% on account of the positive effect of KD therapy in increasing insulin sensitivity.
3. Diminished vascular complications: Due to average 1% decline in HbA1c because of Keto diet, the risk of heart attack has been reported to decrease by 14% and incidence of neuropathy, retinopathy and nephropathy by 37%!

“[The keto diet] is popular because in most cases it can produce very easy and effective weight loss - that’s the primary reason why people start it,” says Los Angeles based Franziska Spritzler, registered dietitian (RD), certified diabetes educator, and founder-author of Low Carb Dietitian. For the frustrated type 2 diabetic, Keto diet is worth a try for a limited 3 months period span.

  

(Please await elaborate details pertaining to KD in the next month's upcoming blog)

DR R K SANGHAVI

Prophesied Enabler

Experience & Expertise: Clinician & Healthcare Industry Adviser

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