Effects of a very low-calorie diet and a very low-carbohydrate high-fat diet on blood sugar markers in type 2 diabetes patients

Abstract

Background: Type 2 diabetes is a serious metabolic disease that is on the rise. There is a high degree of global consensus among the major dietary guidelines for the management of type 2 diabetes. Multiple studies have shown that a 10-15 kg weight loss can normalize blood sugar and lead to type 2 diabetes remission, but little attention is paid to the potential of promoting type 2 diabetes remission in clinical practice today, except with bariatric surgery. The mechanisms for diabetes remission after weight loss are not fully understood, but studies have shown that caloric restriction can result in decreased liver fat content and increased insulin sensitivity. Furthermore, low-carbohydrate high-fat diets have been increasingly recognized as a therapeutic strategy for the management of type 2 diabetes. To manage type 2 diabetes blood glucose should be monitored regularly, the most informative method being continuous glucose monitoring. Data from a continuous glucose monitor (CGM) can be used to estimate time in range (TIR), glycemic variability (GV), estimated A1c (eA1c) and average glucose (AG), which are all measures of blood glucose that can be helpful in the treatment and management of type 2 diabetes. Aim and objectives: The overall aim of this thesis was to evaluate how diet, anthropometric measurements (body weight, BMI, waist circumference (WC) and waist-to-height ratio (WHtR)), fat mass (%) and lifestyle factors (sleep, stress, physical activity) affect blood sugar regulation in individuals with overweight/obesity and type 2 diabetes. Blood sugar markers that were assessed were hemoglobin A1c (HbA1c), AG, eA1c, GV, and TIR. Specific objectives were to determine the associations between baseline blood sugar markers and baseline anthropometric measurements (body weight, BMI, waist circumference (WC) and waist-to-height ratio (WHtR)), age, baseline fat mass (%) and fat free mass (%). How baseline dietary intake, measured by Food Frequency Questionnaire (FFQ), corresponds to the Norwegian dietary guidelines, and is associated with baseline blood sugar markers were also evaluated. Furthermore, the short-term effects (1 –7 days) of a very low-calorie diet (VLCD) and a very low-carbohydrate high-fat (VLCHF) diet on blood sugar regulation measured by continuous glucose monitors were assessed, as well as the effects on HbA1c, measures of adiposity (body weight, BMI, WC, WHtR, and fat mass (%)) and blood lipids (total cholesterol, LDL-C, HDL-C, and TAG) after 3 months on a VLCD or a VLCHF diet. Finally, the relationship of stress, sleep, and physical activity with blood glucose regulation in a group of type 2 diabetes patients was analyzed. Methods: This thesis is based on a subset of data from the ongoing CARBCOUNT study and includes 31 participants that enrolled in the study from January to April 2022. All participants were randomized to a VLCD or a VLCHF diet. The thesis includes both cross-sectional and prospective analyses. The data analyzed in this thesis were collected at the baseline and 3-month visits, including data from blood samples, anthropometric measurements, BOD POD, CGM, Food Frequency questionnaire (FFQ) and other questionnaires (International physical activity questionnaire (IPAQ), Perceived Stress Scale (PSS) and a customized questionnaire about sleep). Results: BMI, WHtR, and waist circumference were inversely correlated with indicators of increased blood sugar and poor blood glucose control (average glucose, HbA1c and GV). Interestingly, blood sugar markers (HbA1c, AG and eA1c) were inversely correlated with intake of sugar and sweets, as well as SFAs. Compared to Norwegian dietary guidelines, the baseline diet of the CARBCOUNT participants was somewhat low in carbohydrates (43 energy percent (E%) and sufficient in fruits, berries, vegetables, wholegrains, and fiber. The median intake of saturated fat was high (12.1 E%), partly caused by a high intake of red meat (699 g/week). The participants achieved improvements in blood sugar markers after 1 week on either dietary intervention. AG decreased by 18.5% in the VLCD group and by 14.8% in the VLCHF group, eA1c by 19.6% in the VLCD group and by 18.4% in the VLCHF group, and GV decreased by 29.4% in the VLCHF group but did not significantly decrease in the VLCD group. TIR did not increase significantly in neither of the dietary groups. Looking at the data of all 18 participants who completed the baseline and 3-month (3M) visits, there were significant improvements in measured parameters (HbA1c, body weight, WC, BMI, WHtR, percent fat mass and TAG) in both dietary groups. No significant changes in total cholesterol, HDL and LDL were found. There were no significant correlations between blood sugar markers and perceived stress, sleep, or physical activity. Conclusion: Results from this thesis demonstrate that only 1 week on a VLCD or a VLCHF diet can lead to substantial improvements in blood sugar parameters. The results also showed that long-term blood sugar (HbA1c) as well as measures of adiposity were significantly improved after 3 months on a VLCD or a VLCHF diet. The improvements in blood sugar parameters were related to weight reduction and improvements in body composition. Underlying mechanisms for the improvement of blood sugar markers caused by VLCD and VLCHF diets need to be further investigated, to achieve better future management and treatment of type 2 diabetes.