Journal für Klinische Endokrinologie und Stoffwechsel Austrian Journal of Clinical Endocrinology and Metabolism 2012; 5 (Sonderheft

Background and aims: Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function. Methods and results: In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35-63 kg/m(2), age 39.4 +/- 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated. GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups. Conclusion: We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Erhöhte Serumspiegel verzweigtkettiger Aminosäuren (BCAA: Valin, Leucin, Isoleucin) bei Insulinresistenz und/oder Typ-2-Diabetes (T2D) können aus den Ernährungsgewohnheiten, der Darmmikrobiomzusammensetzung oder einer zellulären Energiestoffwechselstörung resultieren. Wir prüften die Hypothese, dass eine diätetische BCAA-Reduktion die Insulinsensitivität verbessert und die Insulinsekretion bei Patienten mit T2D vermindert.

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 +/- 1.5 kg/m(2)), age-matched insulin-resistant obese subjects (BMI: 34.3 +/- 1.7 kg/m(2)) and similarly obese elderly T2D patients (BMI: 32.0 +/- 2.4 kg/m(2)) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic gamma ATP, inorganic phosphate (P-i) and lipids using P-31/H-1 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 260 min, 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 (160 min: r= 0.51, 240 min: r = 0.59), and negatively with adipose tissue insulin sensitivity (r = -0.73). Higher meal-induced glucagon release (iAUC(0)(-260) (min)) correlated with lower fasting (r = -0.62) and postprandial P(i )levels (160 min: r = -0.43, 240 min: r = -0.42; all P < 0.05). Higher meal-induced release of GIP (iAUC(0-260) (min)) correlated positively with fasting (r = 0.54) and postprandial serum triglyceride concentrations (iAUC(0-260 min, )r = 0.54; all P < 0.01). Conclusion. - Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic P-i suggest a role for glucagon in hepatic energy metabolism. (C) 2018 Elsevier Masson SAS. All rights reserved.

Journal für Klinische Endokrinologie und Stoffwechsel Austrian Journal of Clinical Endocrinology and Metabolism 2012; 5 (Sonderheft

Glucose effectiveness (S-G) represents the ability of glucose per se, under basal insulin concentrations, to stimulate its own uptake and to suppress its own production. S-G and its two components BIE (Basal Insulin Effect) and GEZI (Glucose Effectiveness at Zero Insulin) are known to decline in subjects whose glycemic status worsens, but no study aimed to analyze whether changes may occur even before, when a normal glucose tolerance status is still preserved but insulin resistance has already arisen. To investigate this issue, S-G, BIE and GEZI were estimated from the minimal model interpretation of frequently sampled intravenous glucose tolerance (FSIGT) test data in two groups of subjects with normal glucose tolerance (basal glycemia < 5.6 mmol/l): a group of control participants (CNT, n=50) and a group of subjects with pathologies or conditions causing insulin resistance (IR, n=50). No difference in mean values of S-G was observed in the IR with respect to the CNT group (2.3 +/- 0.9 vs. 2.5 +/- 0.9 10(-2) min(-1); p = 0.17). BIE was found to be the minor component of S-G in both CNT and IR group. The GEZI component provided a significantly higher proportional contribution to S-G in the IR with respect to CNT (89% vs. 81% of S-G, p <0.0001). In proportion, a significantly lower contribution was provided by BIE in IR group (11 +/- 1 vs. 18 1, p <0.0001). These results indicate that, at the real starting phase of the process of glucose tolerance impairment (reduced insulin action but normal tolerance), no variation in S-G occurs with respect to normality. An increased proportional contribution of GEZI, when BIE declines, may allow the maintenance of normal glucose effectiveness.

Die Inkretin- und Glukagon-Sekretion ist bei Adipositas und Typ-2-Diabetes (T2D) verändert. Der Zusammenhang zwischen zirkulierenden und hepatozellulären Lipiden (HCL), hepatischem Energiestoffwechsel und Sekretion von Glucagon-like Peptide 1 (GLP-1), glukoseabhängigem insulinotropem Peptid (GIP) und Glukagon ist jedoch unklar.

Abstract The aim of the work was to compare the hormonal and the metabolic mechanisms involved in weight loss and remission of T2DM one year after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in morbidly obese type 2 diabetic (T2DM) patients. Insulin sensitivity, insulin secretion, and the gastrointestinal (GI) hormone response to a mixed meal test (MMT) were evaluated before and one year after BS (14 RYGB and 19 VSG). RYGB and VSG groups had similar characteristics at baseline. Weight loss at one year was similar in the 2 groups (ΔBMI%: − 32±10 and − 30±7%, p=0.546). Insulin sensitivity and insulin secretion improved similarly after either procedures with a similar rate in T2DM remission (86% in RYGB and 76% in VSG). Meal-stimulated GLP-1 levels increased after both procedures reaching significantly higher levels after RYGB (p=0.0001). GIP response to MMT decreased to a similar extent after the 2 interventions (p=0.977). Both fasting and post-meal ghrelin concentrations were markedly suppressed after VSG and significantly lower than RYGB (p=0.013 to p=0.035). The improvement of insulin sensitivity and beta-cell function was significantly associated with weight loss (p=0.014 to p=0.035), while no relation was found with the changes in GI hormones. In conclusion, in morbidly obese T2DM patients, RYGB and VSG result in similar improvements of the glucose status in the face of different GI hormonal pattern. Weight loss is the key determinant of diabetes remission one year after surgery.

Abstract 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.

Fragestellung: Adiponektin ist ein Adipokin und assoziiert mit reduziertem Diabetesrisiko. Rezente Daten in Patienten mit Typ 2 Diabetes (T2D) weisen darauf hin, dass sich zum Zeitpunkt der Diabetesmanifestation die Richtung der Assoziation von Adiponektin mit mikro- und makrovaskulären Komplikationen umkehrt. Ziel dieser Studie war daher, Zusammenhänge zwischen Veränderungen von Adiponektin mit Veränderungen des HbA1c, der Insulinsensitivität und -sekretion nach Diabetesdiagnose zu analysieren.

AIMS: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. METHODS:Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n = 42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre-hepatic β-cell function, glucose tolerance index and C-peptide secretion within the first year of diabetes diagnosis and 2 years later. Associations of changes in serum concentrations of total adiponectin, high-molecular-weight adiponectin and their ratio with changes in the aforementioned metabolic variables were calculated using linear regression. RESULTS:Among people with Type 2 diabetes, 2-year increases in high-molecular-weight adiponectin and in high-molecular-weight/total adiponectin ratio were associated with decreases in glucose tolerance index of 0.1%/min (P = 0.020) and 0.8%/min (P = 0.013), respectively. Increases in high-molecular-weight/total adiponectin ratio were related to decreases in acute C-peptide secretion of 54.6% (P = 0.020). Among people with Type 1 diabetes, 2-year increases in total adiponectin were associated with 2-year decreases in acute C-peptide secretion of 56.2% (P = 0.035). CONCLUSIONS:Increases in adiponectin concentrations in the first 2 years after diagnosis were related to a worsening of acute insulin secretion and glucose tolerance index in Type 1 and Type 2 diabetes. (Clinical Trials Registry no.: NCT01055093).

Assoziationen zwischen subklinischer Inflammation und Hyperglykämie sind bei Personen mit Prädiabetes bekannt. Der Einfluss von Biomarkern der subklinischen Inflammation auf die frühe Progression von Patienten mit neu-manifestiertem Typ 1 (T1D) und Typ 2 Diabetes (T2D) ist jedoch noch unzureichend geklärt. Ziel dieser Studie war es daher, Zusammenhänge zwischen Veränderungen der subklinischen Inflammation mit Veränderungen der glykämischen Kontrolle in den ersten zwei Jahren nach Diabetesdiagnose zu analysieren.

Subclinical inflammation is associated with hyperglycemia in pre-diabetic individuals. However, the impact of biomarkers of subclinical inflammation on the early progression of type 1 (T1D) and type 2 diabetes mellitus (T2D) after the diagnosis of the disease remains to be further elucidated.