Aspects on diabetes and diet with special focus on carbohydrates : epidemiological and clinical studies

Carbohydrate intake affects blood glucose levels more than any other dietary factor, providing a conceptually promising area of research in the prevention and management of diabetes. Intake of fruit and vegetables, a mainly carbohydratecontaining food group with low-energy and nutrient-dense content, has shown inconsistent associations with the risk of developing type 2 diabetes (T2D) in prospective cohort studies, and very limited research exists on the association with the risk of developing prediabetes. Current guidelines for the dietary management of type 1 diabetes (T1D) are also very limited. Low carbohydrate diets have shown some promising effects in a few small trials in adults with T1D but their short-term and long-term effects remain to be further investigated. Web-based dietary assessment programs are available to facilitate nutritional research but to ensure the quality of the collected data, these need to be validated first.

The overall aim of this thesis was to investigate the effect of food groups, meals and diets with a focus on their carbohydrate content, on the prevention of prediabetes and T2D and the management of T1D.

In the prospective cohort study I, the aim was to investigate the association between fruit and vegetable intake and the risk of developing prediabetes and T2D in 6961 Swedish men and women over 20-years of follow-up. The results demonstrated an inverse association between higher total fruit and vegetable intake and T2D risk (HR 0.76, 95% CI 0.60, 0.96) and between higher fruit intake and prediabetes risk (HR 0.76, 95% CI 0.58, 1.00), in men but not in women.

In the randomized crossover study II, the aim was to assess the effect of four isocaloric meals with different macronutrient compositions on postprandial blood glucose, lipid, and glucagon levels in 17 adults with T1D, and to compare the effect of the same meals in a control group of 21 healthy subjects. During a 4-hour postprandial period, the two meals with lower carbohydrate content (32-33% of energy), one high in protein and one high in fat, resulted in lower glucose excursions than two isocaloric high-carbohydrate meals (53-54% of energy), one of these including extra fiber. The high-protein meal also resulted in fewer hypoglycemic events and lower postprandial triglyceride excursions compared to the isocaloric high-fat meal. Glucagon concentrations increased more after the high-protein meal. Compared to the control group, the T1D group had higher glycemic peak after all meals.

In the validation study III, the aim was to assess relative validity of the web-based program Nutrition Data in measuring energy and macronutrient intake against 24- hour dietary recalls (24HRs) and evaluate the program’s user acceptability in 42 adults with T1D. Nutrition Data showed comparable dietary intake estimates to interviewer-led 24HRs, high correlations for all intakes and no systematic differences between the two methods. However, limits of agreement were relatively wide. Most participants found Nutrition Data easy and fun to use, helpful for carbohydrate counting and would recommend it to others.

In study IV, the aim was to investigate the effect of three diets with different carbohydrate intake (low 15-20%, moderate 30-40% and high 50-60% of energy from carbohydrates) on insulin requirements, metabolic control and glycemic variability in 102 adults with T1D. The 3-month preliminary results of the randomized controlled trial DANCE showed that insulin requirements were 0.06 IU/kg (95% CI −0.12, 0.0) or 6.5 IU/day (95% CI −12.5, −0.6) lower after the low carbohydrate diet compared to the diet with higher carbohydrate content. These differences were not significant after adjusting for BMI changes. Notably adherence to the low carbohydrate diet was moderate. However, glycemic control and variability measured with continuous glucose monitoring system metrics still improved in the low carbohydrate diet group compared to the high carbohydrate diet, with between-group differences of 12% (95% CI 3, 22) in time in range, −9% (95% CI −21, −2) in time above range and −0.5 mmoL/L (95% CI −1.0, −0.1) in SD of mean sensor glucose, irrespective of BMI changes. There were no significant differences in changes of HbA1c, lipid status, ketone levels, BMI or anthropometrics between diet groups. The moderately low carbohydrate diet did not result in differences in any endpoints compared to the other two diets.

In conclusion, the findings of this thesis support the current recommendations for high intakes of fruit and vegetables in T2D prevention and show an inverse association between high fruit intake and the risk of developing prediabetes, at least in men. For T1D, low carbohydrate meals and diets had a favorable effect on glycemic markers including less variability compared to high-carbohydrate meals and diets, and not in the expense of blood lipids or ketones. Overall, studies I-IV provide new evidence on the effect of diet, with special focus on carbohydrate intake, primarily on the management of T1D and secondarily on the prevention of prediabetes and T2D.

List of scientific papers

I. Ba routi AA, Tynelius P, Lager A, Björklund A. Fruit and vegetable intake and risk of prediabetes and type 2 diabetes: results from a 20-year long prospective cohort study in Swedish men and women. Eur J Nutr. 2022;61(6):3175-3187.
https://doi.org/10.1007/s00394-022-02871-6

II. Ba routi AA, Björklund A, Catrina SB, Brismar K, Rajamand Ekberg N. Effect of Isocaloric Meals on Postprandial Glycemic and Metabolic Markers in Type 1 Diabetes-A Randomized Crossover Trial. Nutrients. 2023;15(14):3092. Published 2023 Jul 10.
https://doi.org/10.3390/nu15143092

III. Ba routi AA, Bonn SE, Björklund A. Validation of a web-based dietary assessment program against 24-hour recalls in adults with type 1 diabetes. [Submitted]

IV. Ba routi AA and Björklund A. A randomized controlled trial on low, moderate and high carbohydrate diet in adults with type 1 diabetes: The DANCE (Diabetes ANd CarbohydratEs) study protocol, baseline characteristics and 3-month preliminary results. [Manuscript]