Nutritional counseling frequency and baseline food pattern predict implementation of a high-protein and high-polyunsaturated fatty acid dietary pattern: 1-year results of the randomized NutriAct trial.

BACKGROUND & AIMS: NutriAct is a 36-month randomized controlled multi-center trial designed to analyze the effects of a food pattern focusing on a high-protein and high-unsaturated fatty acids (UFA) intake on healthy aging. We aimed to determine factors associated with a successful modulation of dietary pattern after 12 months in elderly participants. METHODS: 502 participants were randomized into either usual care control group including dietary recommendations of the German Nutrition Society (DGE) or an intervention group, which used supplementation of rapeseed oil and specifically designed foods as well as repetitive advices to implement a food pattern based on high intake of predominantly plant proteins, UFA and fiber (NutriAct pattern). Food intake was repeatedly assessed by 3-day food records at months 0, 3, 6 and 12. Linear regression models were used to investigate determinants of basal food intake and modulation of dietary pattern during the intervention. RESULTS: Food records of 242 intervention and 246 control participants (median age 66 y, 37% males) were available at baseline and were included. At baseline, high BMI was related to higher protein and saturated fatty acids and lower fiber intake. The intervention resulted in higher intake of protein, mono- and polyunsaturated fatty acids (MUFA and PUFA) and fiber, and lower carbohydrate and saturated fatty acid consumption (all p < 0.001). While individuals who were already at baseline closer to the NutriAct pattern also achieved a diet closer to the proposed pattern at month 12, the strongest absolute changes (%E) of dietary behavior were seen in those with dietary patterns further away from the proposed pattern at baseline. Attendance to nutritional sessions was crucial to change MUFA, PUFA, fiber and carbohydrate intake. CONCLUSIONS: A successful modification of dietary pattern was achieved by the performed intervention within 12 months. Baseline dietary habits and attendance to nutritional sessions were substantial determinants predicting changes in dietary pattern. CLINICAL TRIAL REGISTRATION: The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.

[New Developments in Type 1 Diabetes]. / Neue Entwicklungen bei Diabetes mellitus Typ 1.

MONITORING: With the increasing prevalence of continuous glucose monitoring (CGM) systems, time in range (TIR) is gaining importance as a parameter for optimization of glycemic control in patients with type 1 diabetes mellitus. Recent studies showed improved prevention of cardiovascular events and pregnancy complications in patients with optimized TIR. In addition to TIR, it is recommended to consider Time below Range (TBR) as well to include an assessment of hypoglycemia. HYPOGLYCEMIA: Hypoglycemia remains a clinically relevant complication of therapy for type 1 diabetes mellitus. With the approval of nasal glucagon, there is now an alternative to traditional injections as an easy-to-use emergency therapy. With the development of the glucagon analogue Dasiglucagon, which is stable in the liquid state, a classic emergency pen with a ready-to-use solution will also potentially be available in the near future. INSULIN THERAPY: The new fast-acting insulin aspart (FIASP) offers new opportunities for blood glucose optimization in type 1 diabetes patients. Furthermore, the first hybrid closed-loop system for the treatment of type 1 diabetes mellitus was approved in Germany in 2019. This system automatically adjusts the basal rate based to blood glucose levels measured by CGM. When used adequately, a hybrid closed-loop system allows for improved glycemic control, particularly of nocturnal blood glucose. COMPLEMENTARY THERAPIES: Since 2019, the SGLT-2 inhibitor dapagliflozin and the combined SGLT-1/2 inhibitor sotagliflozin have been approved for the therapy of inadequately controlled type 1 diabetics with a BMI above 27 kg/m² and no elevated risk of diabetic ketoacidosis. The most relevant side effect is atypical normoglycemic ketoacidosis, which is why initial risk assessment and adequate training of the patient to perform and interpret ketone body and pH measurements during therapy are of central importance.

Caloric restriction chronically impairs metabolic programming in mice.

Although obesity rates are rapidly rising, caloric restriction remains one of the few safe therapies. Here we tested the hypothesis that obesity-associated disorders are caused by increased adipose tissue as opposed to excess dietary lipids. Fat mass (FM) of lean C57B6 mice fed a high-fat diet (HFD; FMC mice) was "clamped" to match the FM of mice maintained on a low-fat diet (standard diet [SD] mice). FMC mice displayed improved glucose and insulin tolerance as compared with ad libitum HFD mice (P < 0.001) or SD mice (P < 0.05). These improvements were associated with fewer signs of inflammation, consistent with the less-impaired metabolism. In follow-up studies, diet-induced obese mice were food restricted for 5 weeks to achieve FM levels identical with those of age-matched SD mice. Previously, obese mice exhibited improved glucose and insulin tolerance but showed markedly increased fasting-induced hyperphagia (P < 0.001). When mice were given ad libitum access to the HFD, the hyperphagia of these mice led to accelerated body weight gain as compared with otherwise matched controls without a history of obesity. These results suggest that although caloric restriction on a HFD provides metabolic benefits, maintaining those benefits may require lifelong continuation, at least in individuals with a history of obesity.

Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21.

OBJECTIVE: Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator-activator receptor (PPAR) alpha-dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPARalpha, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS: The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPARgamma activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS: Oleate and linoleate increased FGF-21 expression and secretion in a PPARalpha-dependent fashion, as demonstrated by small-interfering RNA-induced PPARalpha knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS: The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity.

An accurate risk score based on anthropometric, dietary, and lifestyle factors to predict the development of type 2 diabetes.

OBJECTIVE: We aimed to develop a precise risk score for the screening of large populations for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study populations. RESEARCH DESIGN AND METHODS: A prospective cohort study (European Prospective Investigation into Cancer and Nutrition [EPIC]-Potsdam study) of 9,729 men and 15,438 women aged 35-65 years was used to derive a risk score predicting incident type 2 diabetes. Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score. Data from the EPIC-Heidelberg, the Tübingen Family Study for Type 2 Diabetes (TUF), and the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study were used to validate this score. RESULTS: Information on age, waist circumference, height, history of hypertension, physical activity, smoking, and consumption of red meat, whole-grain bread, coffee, and alcohol formed the German Diabetes Risk Score (mean 446 points [range 118-983]). The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3% for 300 to 23.2% for 750 score points. The area under the receiver-operator characteristic (ROC) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies. Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were -0.56 in the TUF and -0.45 in the MeSyBePo studies. ROC values for undiagnosed diabetes were 0.83 in the TUF and 0.75 in the MeSyBePo studies. CONCLUSIONS: The German Diabetes Risk Score (available at www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes.

Frataxin deficiency in pancreatic islets causes diabetes due to loss of beta cell mass.

Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing beta cells. We have disrupted expression of the mitochondrial protein frataxin selectively in pancreatic beta cells. Mice were born healthy but subsequently developed impaired glucose tolerance progressing to overt diabetes mellitus. These observations were explained by impairment of insulin secretion due to a loss of beta cell mass in knockout animals. This phenotype was preceded by elevated levels of reactive oxygen species in knockout islets, an increased frequency of apoptosis, and a decreased number of proliferating beta cells. Hence, disruption of the frataxin gene in pancreatic beta cells causes diabetes following cellular growth arrest and apoptosis, paralleled by an increase in reactive oxygen species in islets. These observations might provide insight into the deterioration of beta cell function observed in different subtypes of diabetes in humans.