|Year : 2017 | Volume
| Issue : 5 | Page : 776-780
Effect of a low-calorie diet on restoration of normoglycemia in obese subjects with type 2 diabetes
Anjali Amit Bhatt1, Priya K Choudhari2, Rutuja R Mahajan2, Mehmood G Sayyad3, Devi D Pratyush4, Imtiaz Hasan5, Rajesh S Javherani1, Manish M Bothale1, Vedavati B Purandare1, Ambika Gopalakrishnan Unnikrishnan1
1 Department of Clinical Diabetology and Endocrinology, Chellaram Diabetes Institute, Pune, Maharashtra, India
2 Department of Dietetics and Nutrition, Chellaram Diabetes Institute, Pune, Maharashtra, India
3 Department of Biostatistics, Chellaram Diabetes Institute, Pune, Maharashtra, India
4 Department of Research, Chellaram Diabetes Institute, Pune, Maharashtra, India
5 Department of Pathology, Chellaram Diabetes Institute, Pune, Maharashtra, India
|Date of Web Publication||15-Sep-2017|
Ambika Gopalakrishnan Unnikrishnan
Department of Clinical Diabetology and Endocrinology, Chellaram Diabetes Institute, Lalani Quantum, Pune-Bangalore Highway, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Type 2 diabetes mellitus (T2DM) is considered to be an inevitably progressive disease. Complex therapies add to the financial and psychological burden. Very low-calorie diets (LCDs) are emerging as an option in the management of type 2 diabetes. Methods: We performed a clinical audit of patients with T2DM who received 12 weeks of LCD. Results: This case series documents that 6 out of 12 participants (median baseline HbA1c 9%) achieved HbA1c level in nondiabetes range with LCD despite stopping all antidiabetes medications. There was an improvement in serum triglycerides, HDL cholesterol, total cholesterol, C-Reactive protein, urine microalbumin, liver transaminases, liver fat and the indices of insulin resistance, beta cell secretory capacity, and insulin sensitivity. Conclusion: If long-term follow-up proves sustained benefits, such dietary restriction may be an alternative to more drastic options for reversal of type 2 diabetes. This may also help in changing the treatment perspective of a newly detected T2DM from an incurable and inevitably progressive disease to a potentially reversible disease.
Keywords: Nutrition, obesity, reversal, type 2 diabetes, very low-calorie diet
|How to cite this article:|
Bhatt AA, Choudhari PK, Mahajan RR, Sayyad MG, Pratyush DD, Hasan I, Javherani RS, Bothale MM, Purandare VB, Unnikrishnan AG. Effect of a low-calorie diet on restoration of normoglycemia in obese subjects with type 2 diabetes. Indian J Endocr Metab 2017;21:776-80
|How to cite this URL:|
Bhatt AA, Choudhari PK, Mahajan RR, Sayyad MG, Pratyush DD, Hasan I, Javherani RS, Bothale MM, Purandare VB, Unnikrishnan AG. Effect of a low-calorie diet on restoration of normoglycemia in obese subjects with type 2 diabetes. Indian J Endocr Metab [serial online] 2017 [cited 2018 Nov 17];21:776-80. Available from: http://www.ijem.in/text.asp?2017/21/5/776/214781
| Introduction|| |
Type 2 diabetes mellitus (T2DM) has long been considered as an inevitably progressive disease irrespective of the evolvement in pharmacological strategies. Patients are expected to accept the diagnosis of a lifelong disease requiring sequentially increasing pharmacotherapy. Pharmacotherapy has not only added to the increasing cost of treatment but has also failed to permanently alter the pathophysiology of the disease. Contrary to this belief, recent clinical studies have shown that reversal of diabetes is possible with a calorie-restricted diet without using any pharmacological therapy. It is also seen that there is a sustainable return to normalcy of beta cell function, hepatic glucose output, and visceral fat by acute restriction of dietary energy intake in individuals with T2DM.,,, Indeed, effect of acute food restriction has been compared with the glycemic improvement after bariatric surgery.
We hereby present findings of a clinical audit on patients with T2DM who received 12-week low-calorie diet (LCD) as a part of their therapeutic plan. High rates of diabetes reversal in newly diagnosed Indian adults with T2DM are reported with intensive lifestyle therapy. To our knowledge, there has been no experience of LCD (~1000 kcal/day) in type 2 diabetes from India.
| Methods|| |
A clinical audit was performed on the profile of 12 patients with T2DM who willingly enrolled for an LCD program for 12 weeks (The details of the program are described below). After a full discussion of the pros and cons of LCD, patients had been started on a specific dietary program consisting of 1000 kcal/day diet using meal replacement protein formula [Prototal Whey; containing 378.5 kcal, 48 g whey protein, 41 g of carbohydrate, and 2.5 g of fat along with micronutrients [Supplementary Table 1]. The total daily calories of 1000 kcal/day were achieved by giving three servings of 30 g formula with 150 ml of skimmed milk in addition to one regular meal and 2–3 small prespecified homemade snacks. The approximate nutritive values of sample dietary plan for a day are shown in [Table 1]. This meal plan constituted around 60% energy from carbohydrate, 30% energy from protein, and 10% energy from fat. The recipes of all homemade snacks with exact measurement of raw material were provided. Care was taken to provide at least 3 L of fluid/day.
|Table†1: Approximate nutritive values of sample dietary plan for a day during low-calorie diet therapy|
Click here to view
All antidiabetes medications had been stopped in all but two participants who were both on basal bolus regimen of insulin in addition to three oral antidiabetes medications (metformin, sulfonylurea, and gliptin). These two patients continued to take metformin and basal insulin; meal-related insulin and other oral antidiabetes agents were stopped. Reduction in doses of metformin and basal insulin was done as necessary during LCD therapy. Statin therapy was continued in those who were taking it before the LCD therapy. Antihypertensive medications had been titrated as required during the due course. Home blood glucose monitoring with glucometer was done by testing fasting and 2 h post breakfast, lunch, and dinner on alternate days. Telephonic or E-mail follow-ups by nutritionists were done on a weekly basis to ensure compliance. Anthropometric parameters were collected monthly. Clinical and biochemical parameters were monitored monthly by a physician to detect any inadvertent occurrence of dyselectrolytemia, hyperuricemia, or gall stones. All participants were also advised moderate intensity aerobic and resistance exercise from the 2nd week after starting on LCD.
| Results|| |
We categorized participants as “Responders” (n = 6) and “Nonresponders” (n = 6) with respect to the improvement in HbA1c to nondiabetes range, i.e., an HbA1c below 6.5% without medications was classified as “responder”. All participants (n = 12) had a significant fall in their HbA1c (median HbA1c dropped from 9% to 6.2%) after 12 weeks of LCD. Fifty percent (n = 6) of the participants had their HbA1c in nondiabetes range with all glucose control medication being stopped [Table 2]. In terms of median value, responders were younger with shorter duration of diabetes and needed less treatment for diabetes compared to nonresponders; two of the nonresponders were on basal bolus insulin at baseline. Responders also had marginally higher BMI and waist circumference but slightly lower HbA1c than nonresponders. There was a greater (30%) reduction in the median HbA1c of the responders compared to nonresponders (21%) with similar reduction in weight. Both responders as well as nonresponders demonstrated a fall in fasting and postmeal blood glucose levels. Nonresponders were also able to reduce the number of antidiabetes medicines including insulin doses. There was 50% reduction in insulin dose in one participant, whereas the other one was totally free of insulin at the end of 12 weeks. There was also a significant reduction in serum levels of liver transaminases in responders and improvement in liver fat measured by ultrasound (detailed result provided in supplement). Nonresponders had higher levels of insulin resistance (measured as HOMA-IR by HOMA2 model), lesser beta cell secretory capacity (measured as HOMA-β by HOMA2 model) as well as lesser insulin sensitivity (measured as QUICKI score) at baseline [Figure 1]. Overall, there was an improvement in HOMA-IR, HOMA-β, and QUICKI score after 12 weeks of LCD in both responders as well as nonresponders. There was no unfavorable change in the nutritional parameters including hemogram, electrolytes, uric acid, serum proteins, and serum levels of Vitamin B12. There were no events of symptomatic hypoglycemia, and no participant experienced symptoms such as excessive hunger or lethargy showing that all participants tolerated the diet plan well. Detailed characteristics of individual participants are provided as [Supplementary Table 1] [Additional file 1] and [Supplementary Table 2] [Additional file 2].
|Table†2: The comparison of all parameters studied in responders and nonresponders|
Click here to view
|Figure 1: Changes in HbA1c and glycemic indices in responders and nonresponders|
Click here to view
| Discussion|| |
This case series documents that half of the participants with a significant baseline hyperglycemia (median HbA1c 9%) achieved HbA1c level in the nondiabetes range (<6.5%) at the end of 12 weeks of LCD therapy (P < 0.001) without need for antidiabetes medications. All except two patients in the nonresponder group showed improvement in the indices of insulin resistance, beta cell secretory capacity, and insulin sensitivity [Figure 1]a,[Figure 1]b,[Figure 1]c,[Figure 1]d,[Figure 1]e,[Figure 1]f,[Figure 1]g,[Figure 1]h,[Figure 1]i,[Figure 1]j. The responders had a shorter duration of diabetes and needed lesser antidiabetes medications at the baseline suggesting that LCD works better if it is started earlier in the course of the disease. Although the diet was not carbohydrate restricted (energy from carbohydrate 60%), a balanced protein intake with the help of formula meal during LCD may be more effective in Indian participants who consume predominately high carbohydrate meals. The results are similar to “the Counterpoint study” (Counteracting Pancreatic Inhibition by Triglyceride) from the UK where dramatic effects on diabetes reversal were observed by giving very low-calorie diet (VLCD – 400–600 kcal/day) in the form of liquid meal formula with nonstarchy vegetables and salads for 8 weeks. Our study suggests that such results may also be achieved with a more practical and acceptable LCD (1000 kcal/day). It is proposed that this state of acute energy crisis necessitates the utilization of the excess circulating glucose with corresponding improvement in insulin sensitivity as well as beta cell secretory capacity as measured by clamp studies. It also results in the reduction of triglyceride stored in the liver as measured by magnetic resonance imaging.,,
The follow up “Counterbalance study” (Counteracting BetA cell failure by Long-term Action to Normalize Calorie intakE) has shown that the result of VLCD is not only acute but also result in sustained (6 months after completion of 8-weeks therapy in this study) glycemic normalcy with pathophysiologic changes in metabolism of patients with diabetes even after reintroduction of isocaloric diet. The reduction in hepatic fat was sustained with no redistribution of fat to the liver from the subcutaneous deposits even after 6 months of weight maintenance even though the participants did not attain weight normalcy. The second major change VLCD brings about is the reduction in pancreatic fat with recovery of first phase insulin secretion to nondiabetes levels., It was also observed that the nonresponders were characterized by evidence of insulin deficiency at baseline and lack of ability to regenerate insulin secretion capacity. Our study could not observe this differentiation mainly because of a small sample size and HOMA2 indices done in our study being less accurate compared to clamp studies. Notably, all our participants were obese as per the Asia-specific BMI cutoff (>25 kg/m2). In general, our study may reflect the benefit of LCD in obese type 2 diabetes. However, for obvious reasons, LCD may not benefit lean participants with recent weight loss and osmotic symptoms. Furthermore, participants with coexisting severe systemic illness would not be appropriate candidates for LCD therapy.
This study has many limitations. The most important is a small sample size, but the effect size of glycemic reduction is large, thus making the results significant. Second, advanced metabolic studies such as clamp study were not performed, but other studies performing clamp studies have shown similar results. A longer duration follow-up would be helpful in proving the sustainability of the results.
| Conclusion|| |
Once long-term follow-up studies prove sustained benefits, such dietary restriction may be an alternative to more drastic options such as medications, injections, or metabolic surgery for reversal of type 2 diabetes. These results have important implications in changing the perspective of a newly detected T2DM from an incurable and inevitably progressive disease to a potentially reversible disease, especially in those who are willing to do intense changes in their lifestyle.
Ms. Shraddha Mahajan for help in data entry.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
King P, Peacock I, Donnelly R. The UK prospective diabetes study (UKPDS): Clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol 1999;48:643-8.
Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: Normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011;54:2506-14.
Steven S, Hollingsworth KG, Al-Mrabeh A, Avery L, Aribisala B, Caslake M, et al.
Very low-calorie diet and 6 months of weight stability in type 2 diabetes: Pathophysiological changes in responders and nonresponders. Diabetes Care 2016;39:808-15.
Taylor R. Banting Memorial lecture 2012: Reversing the twin cycles of type 2 diabetes. Diabet Med 2013;30:267-75.
Liu C, Li C, Chen J, Liu Y, Cheng Q, Xiang X, et al.
Effects of a very low-calorie diet on insulin sensitivity and insulin secretion in overweight/obese and lean type 2 diabetes patients. Diabetes Metab 2015;41:513-5.
Snel M, Jonker JT, Hammer S, Kerpershoek G, Lamb HJ, Meinders AE, et al.
Long-term beneficial effect of a 16-week very low calorie diet on pericardial fat in obese type 2 diabetes mellitus patients. Obesity (Silver Spring) 2012;20:1572-6.
Knop FK, Taylor R. Mechanism of metabolic advantages after bariatric surgery: It's all gastrointestinal factors versus it's all food restriction. Diabetes Care 2013;36 Suppl 2:S287-91.
Sarathi V, Kolly A, Chaithanya HB, Dwarakanath CS. High rates of diabetes reversal in newly diagnosed Asian Indian young adults with type 2 diabetes mellitus with intensive lifestyle therapy. J Nat Sci Biol Med 2017;8:60-63.
Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998;21:2191-2.
Hrebícek J, Janout V, Malincíkov√° J, Hor√°kov√° D, Cízek L. Detection of insulin resistance by simple quantitative insulin sensitivity check index QUICKI for epidemiological assessment and prevention. J Clin Endocrinol Metab 2002;87:144-7.
Goday A, Bellido D, Sajoux I, Crujeiras AB, Burguera B, Garcia-Luna PP, et al.
Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr Diabetes 2016;6:e230.
Malandrucco I, Pasqualetti P, Giordani I, Manfellotto D, De Marco F, Alegiani F, et al.
Very-low-calorie diet: A quick therapeutic tool to improve √ü cell function in morbidly obese patients with type 2 diabetes. Am J Clin Nutr 2012;95:609-13.
Taylor R. Type 2 diabetes: Etiology and reversibility. Diabetes Care 2013;36:1047-55.
[Table 1], [Table 2]