Katharina S. Weber

The Role of Markers of Low-Grade Inflammation for the Early Time Course of Glycemic Control, Glucose Disappearance Rate, and β-Cell Function in Recently Diagnosed Type 1 and Type 2 Diabetes.

OBJECTIVE Inflammatory processes are involved in the progression of insulin resistance and β-cell dysfunction in individuals with prediabetes and contribute to the development of diabetes. We hypothesized that higher levels of biomarkers of low-grade inflammation are associated with the early progression of recently diagnosed diabetes. RESEARCH DESIGN AND METHODS Within the prospective German Diabetes Study, patients with recently diagnosed type 1 (n = 42) and type 2 (n = 94) diabetes underwent detailed metabolic characterization within the first year after diagnosis and 2 years thereafter. Associations between changes in markers of low-grade inflammation with changes in glycemic control, β-cell function, and glucose disappearance rate were assessed using multivariable linear regression analysis. Associations were adjusted for age, sex, BMI, smoking status, and 2-year changes in BMI, smoking status, and glucose-lowering medication. RESULTS Patients with type 1 and type 2 diabetes exhibited good glucometabolic control at baseline (mean HbA1c 7.08 ± 1.58% [54 ± 17 mmol/mol] and 6.43 ± 0.98% [47 ± 11 mmol/mol], respectively) and 2 years thereafter (mean HbA1c 7.03 ± 1.20% [53 ± 13 mmol/mol] and 6.62 ± 1.14% [49 ± 13], respectively). Two-year increases of high-sensitivity C-reactive protein, soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 in type 2 diabetes and of IL-18 in type 1 diabetes were associated with 2-year increases of HbA1c. Additionally, 2-year increases of sE-selectin were associated with 2-year decreases of prehepatic β-cell function in type 2 diabetes (all P < 0.05). CONCLUSIONS These data indicate that with the clinical onset of diabetes, low-grade inflammation relates to worsening of glycemia and that endothelial activation may contribute to decreasing β-cell function.

Type 1 Diabetes Mellitus and Exercise in Competitive Athletes

AIMS The number of patients with type 1 diabetes mellitus who are actively participating in competitive sports is increasing. Here, we aimed to assess individual experiences of competitive athletes with type 1 diabetes and to compare these experiences with current recommendations. METHODS A survey of 20 competitive athletes with type 1 diabetes, categorized as endurance (n=10) and non-endurance (n=10) athletes, was performed. RESULTS Endurance and non-endurance athletes did not differ in gender distribution, age, body mass index, and known diabetes duration. Self-reported target blood glucose values prior to exercise were lower in non-endurance than in endurance athletes (195±34 vs. 137±28 mg/dl, P=0.001). The majority of all athletes experienced activity-induced hypo- and hyperglycemic events, independently of exercise type. However, endurance athletes used additional carbohydrate units to prevent activity-induced hypoglycemic events more frequently without monitoring their blood glucose levels than non-endurance athletes (50% vs. 0%, P=0.01). The reduction of the insulin dose on training and competition days compared to days without exercise was similar for endurance and non-endurance athletes. CONCLUSION These results point to a very individual adaption of the athletes therapy during training and competition. However, there are distinct differences in diabetes management between endurance and non-endurance athletes.

Circulating adiponectin concentration is inversely associated with glucose tolerance and insulin secretion in people with newly diagnosed diabetes

To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and β‐cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus.

The Impact of Dietary Factors on Glycemic Control, Insulin Sensitivity and Secretion in the First Years after Diagnosis of Diabetes

BACKGROUND Dietary factors play an important role in the prevention of diabetes mellitus. We tested the hypothesis that dietary factors related to diabetes onset also associate with its progression, i. e., early time courses of insulin sensitivity and secretion in both type 1 and type 2 diabetes. METHODS In a prospective observational study, well-controlled recent-onset diabetes patients (n=127) underwent detailed metabolic characterization within the first year after diagnosis. A follow-up was conducted 2 years after the first examination. Insulin secretion and sensitivity were assessed by intravenous glucose tolerance testing. Baseline food consumption was analyzed by a food propensity questionnaire. Multivariate linear regression analysis was used to assess associations between consumption frequencies at baseline with metabolic changes during the first 2 years. RESULTS Within the first 2 years, metabolic control did not change in patients with type 1 and type 2 diabetes on average. In type 1 diabetes, an increased consumption frequency of refined grains by one time/day at baseline associated with higher HbA1c by 0.60% (95% CI: 0.04; 1.16), P=0.04 after 2 years compared to baseline. In type 2 diabetes, an increased consumption frequency of meat/meat products by one time/day at baseline associated with lower beta-cell adaptation index (-7.25% (95% CI: -13.16; -0.93), P=0.03) after adjustment for age, sex, BMI, and changes of BMI and glucose-lowering medication. CONCLUSION Dietary factors associate with the initial course of diabetes. Reduced consumption of refined grains in type 1 diabetes and of meat products in type 2 diabetes may contribute to preservation of insulin secretion and sensitivity.

Do dogs sense hypoglycaemia

To summarize the current knowledge on the phenomenon of dogs, both trained and untrained, sensing hypoglycaemia and alerting their owners to it.

Habitual Fructose Intake Relates to Insulin Sensitivity and Fatty Liver Index in Recent-Onset Type 2 Diabetes Patients and Individuals without Diabetes

The association between the amount and sources of fructose intake with insulin sensitivity and liver fat needs further elucidation. This study aimed at examining whether habitual intake of sucrose plus non-sucrose bound as well as of non-sucrose bound fructose (total fructose, fruit-derived, juice-derived, sugar sweetened beverages (SSB)-derived fructose) is cross-sectionally associated with insulin sensitivity and fatty liver index (FLI). Fructose intake was estimated using the EPIC food frequency questionnaire from 161 participants with type 2 diabetes (T2D) in the ongoing German Diabetes Study (GDS) (age 53 ± 9 years; HbA1c 6.4 ± 0.9%) and 62 individuals without diabetes (CON) (47 ± 14 years; 5.3 ± 0.3%). Peripheral (M-value) and hepatic insulin resistance were assessed by hyperinsulinemic-euglycemic clamps with stable isotope dilution. FLI was calculated based on body mass index, waist circumference, triglyceride and gamma glutamyl transferase concentrations. Multivariable linear regression analyses were performed. A doubling of SSB-derived sucrose plus non-sucrose bound as well as of non-sucrose bound fructose intake was independently associated with a reduction of the M-value by −2.6% (−4.9; −0.2) and −2.7% (−5.2; −0.1) among T2D, respectively, with an increase in the odds of fatty liver by 16% and 17%, respectively among T2D (all p < 0.05). Doubling fruit-derived sucrose plus non-sucrose bound fructose intake independently related to a reduction in the odds of fatty liver by 13% (p = 0.033) among T2D. Moderate SSB-derived fructose intake may detrimentally affect peripheral insulin sensitivity, whereas fruit-derived fructose intake appeared beneficial for liver fat content.

Positive Effects of Practical Nutrition Lessons in a Primary School Setting with a High Proportion of Migrant School Children

BACKGROUND Children with migration background are at increased risk for overweight, partly due to less favorable dietary habits compared to their German counterparts. We examined the effects of practical nutrition lessons among children with a high proportion of migration background in a primary school setting. METHODS Ten 3rd and 4th grade classes (n=166 children, 73% with migration background) received the intervention and nine school classes (n=139 children, 76% with migration background) served as control. Before, shortly after (only among the intervention group) and three months after the three-day practical nutrition lessons, the nutrition-related skills, behavior, attitudes, and knowledge of the children were assessed using a questionnaire. Changes between baseline and 1st follow-up among children of the intervention group were calculated using linear mixed models. Differences between the two groups for changes between baseline and 2nd follow-up were tested using linear regression analyses. Models were adjusted for potential confounders. RESULTS Shortly after the practical nutrition lessons, the children of the intervention group had improved their knowledge (β=1.7; 95% CI: 1.0; 2.4, P<0.001) and skills (β=1.8; 95% CI: 1.4; 2.2, P<0.001). These changes were sustainable and larger in the intervention compared to the control group (knowledge: β=1.6; 95% CI: 0.7; 2.5, P<0.001; skills: β=1.3; 95% CI: 0.7; 1.9, P<0.001). Changes in nutrition-related behavior and attitudes did not differ between the groups. CONCLUSIONS Providing practical nutrition lessons in a primary school setting with a high proportion of children with immigrational background improved the childrens nutrition-related knowledge and skills.

Cognitive Function Is Impaired in Patients with Recently Diagnosed Type 2 Diabetes, but Not Type 1 Diabetes

Objective To test whether cognitive function is impaired in early states of diabetes and to identify possible risk factors for cognitive impairment. Methods A cross-sectional analysis within the German Diabetes Study included patients with type 1 or type 2 diabetes within the first year after diagnosis or five years after study inclusion and metabolically healthy individuals. Participants underwent comprehensive metabolic phenotyping and testing of different domains of cognitive function. Linear regression models were used to compare cognition test outcomes and to test associations between cognitive function and possible influencing factors within the groups. Results In participants with recently diagnosed diabetes, verbal memory was poorer in patients with type 2 diabetes (P = 0.029), but not in type 1 diabetes (P = 0.156), when compared to healthy individuals. Five years after diagnosis, type 2 diabetes patients also showed lower verbal memory than those with type 1 diabetes (P = 0.012). In addition to crystallized intelligence, a higher body mass index among individuals with recently diagnosed type 2 diabetes and male sex among individuals with recently diagnosed type 1 diabetes were associated with impaired verbal memory (all P < 0.05). Conclusion Verbal memory is impaired in individuals with recently diagnosed type 2 diabetes and likely associated with higher body mass. This trial is registered with the trial registration number NCT01055093.

Meal-derived glucagon responses are related to lower hepatic phosphate concentrations in obesity and type 2 diabetes

AIM Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear. METHODS In this observational study, lean insulin-sensitive control subjects (BMI: 23.2±1.5kg/m2), age-matched insulin-resistant obese subjects (BMI: 34.3±1.7kg/m2) and similarly obese elderly T2D patients (BMI: 32.0±2.4kg/m2) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic γATP, inorganic phosphate (Pi) and lipids using 31P/1H magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration-time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids. RESULTS MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P<0.001), while glucagon concentrations were comparable across all three groups. At 260min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r=0.60) and postprandial hepatocellular lipid levels (160min: r=0.51, 240min: r=0.59), and negatively with adipose tissue insulin sensitivity (r=-0.73). Higher meal-induced glucagon release (iAUC0-260min) correlated with lower fasting (r=-0.62) and postprandial Pi levels (160min: r=-0.43, 240min: r=-0.42; all P<0.05). Higher meal-induced release of GIP (iAUC0-260min) correlated positively with fasting (r=0.54) and postprandial serum triglyceride concentrations (iAUC0-260min, r=0.54; all P<0.01). CONCLUSION Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic Pi suggest a role for glucagon in hepatic energy metabolism.

Positive Effects of Promoting Physical Activity and Balanced Diets in a Primary School Setting with a High Proportion of Migrant School Children.

Background Children with migration background are at particular risk for overweight. We assessed the effects of a primary school-based initiative targeted at enhancing physical activity and dietary education among children with a high proportion of migration background. Methods Four 3rd and 4th grade classes (n=70 children, 77% with migration background) participated in a 10-months intervention comprising 2 additional exercise lessons weekly and 10 nutrition lessons per school year. 6 school classes (n=125 children, 65% with migration background) served as control. Before and after the intervention, an assessment of physical fitness and motor skills and questionnaires on dietary behavior and knowledge were conducted. In a subgroup (n=37), after 6 months of the intervention, daily physical activity was assessed by accelerometer-based monitoring. Differences in changes between the groups were assessed using linear regression analyses. Results Changes between the 2 time points for fitness and motor skill tests (differences in standard deviation scores) were larger in the intervention than in the control group for the total mean test value (β=0.38, p<0.001), driven by higher improvements in 5 of the 8 test items, i.e., obstacle race (speed) (β=0.22, p=0.049), standing long jump (strength) (β=0.35, p<0.001), sit-ups (strength) (β=0.33, p=0.002), stand and reach (mobility) (β=0.22, p=0.042), and 6 min run (endurance) (β=0.40, p<0.001), independently of confounders. Changes in dietary knowledge and consumption frequencies did not differ between groups. Conclusions Promoting guided physical activity in a primary school setting with a high proportion of children with migration background positively affected parameters of fitness and motor skills.