| 1. |
- Manell, Hannes, et al.
(författare)
-
Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes
- 2016
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:3, s. 1181-1189
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).OBJECTIVE: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.DESIGN: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).SETTING: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.PATIENTS AND PARTICIPANTS: Adolescents with obesity, age 10-18 years, with normal glucose tolerance (NGT, n = 23), impaired glucose tolerance (IGT, n = 19), or T2DM (n = 4) and age-matched lean adolescents (n = 19) were included.MAIN OUTCOME MEASURES: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.RESULTS: Adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT (0.25 vs 0.53 pM, P < .05; 18.2 vs 23.6 pM, P < .01) and adolescents with obesity and T2DM had higher fasting glucagon levels (18.1 vs 10.1 pM, P < .01) than those with NGT. During OGTT, glicentin/glucagon ratios were lower in adolescents with obesity and NGT than in lean adolescents (P < .01) and even lower in IGT (P < .05) and T2DM (P < .001).CONCLUSIONS: Obese adolescents with IGT have lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, whereas GLP-1 and glicentin levels are maintained low. During OGTT, adolescents with obesity have more products of pancreatically than intestinally cleaved proglucagon (ie, more glucagon and less GLP-1) in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Paulmichl, Katharina, et al.
(författare)
-
Modification and Validation of the Triglyceride-to-HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus : The Single Point Insulin Sensitivity Estimator (SPISE)
- 2016
-
Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 62:9, s. 1211-1219
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance; because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS: Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and chi(2) test. RESULTS: The novel formula for SPISE was computed as follows: SPISE = 600 X HDL-C-0.185/(TG(0.2) X BMI1.338), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m(2)). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg . kg(-1) . min(-1) (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment insulin resistance) when calculated with M-values. CONCLUSIONS: The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults.
|
|
| 5. |
- Staaf, Johan, et al.
(författare)
-
Initial hyperinsulinemia and subsequent beta-cell dysfunction is associated with elevated palmitate levels
- 2016
-
Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 80:2, s. 267-274
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The prevalence of obesity-related diabetes in childhood is increasing and circulating levels of nonesterified fatty acids may constitute a link. Here, the association between palmitate and insulin secretion was investigated in vivo and in vitro.METHODS: Obese and lean children and adolescents (n = 80) were included. Palmitate was measured at fasting; insulin and glucose during an oral glucose tolerance test (OGTT). Human islets were cultured for 0 to 7 d in presence of 0.5 mmol/l palmitate. Glucose-stimulated insulin secretion (GSIS), insulin content and apoptosis were measured.RESULTS: Obese subjects had fasting palmitate levels between 0.10 and 0.33 mmol/l, with higher average levels compared to lean subjects. While obese children with elevated palmitate (>0.20 mmol/l) had accentuated insulin levels during OGTT, obese adolescents with high palmitate had delayed first-phase insulin response. In human islets exposed to palmitate for 2 d GSIS was twofold enhanced, but after 7 d attenuated. Intracellular insulin content decreased time-dependently in islets cultured in the presence of palmitate and cleaved caspase 3 increased.CONCLUSION: The rapid accentuated and delayed insulin secretory responses observed in obese children and adolescents, respectively, with high palmitate levels may reflect changes in islet secretory activity and integrity induced by extended exposure to the fatty acid.
|
|
