期刊
DIABETES CARE
卷 41, 期 8, 页码 1696-1706出版社
AMER DIABETES ASSOC
DOI: 10.2337/dc18-0244
关键词
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资金
- National Institutes of Health [U01-DK-094406, U01-DK-094430, U01-DK-094431, U01-DK-094438, U01-DK-094467, P30-DK-017047, P30-DK-020595, P30-DK-045735, P30-DK-097512, UL1-TR-000430, UL1-TR-001082, UL1-TR-001108, UL1-TR-001855, UL1-TR-001857, UL1-TR-001858, UL1-TR-001863]
- Department of Veterans Affairs
- Kaiser Permanente Southern California
- American Diabetes Association
- Allergan
- Apollo Endosurgery
- Abbott Laboratories
- Novo Nordisk
OBJECTIVE To compare insulin sensitivity (M/I) and-cell responses in youth versus adults with impaired glucose tolerance (IGT) or drug-naive, recently diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS In 66 youth (80.3% with IGT) and 355 adults (70.7% IGT), hyperglycemic clamps were used to measure 1) M/I, 2) acute (0-10 min [first phase]) C-peptide (ACPR(g)) and insulin (AIR(g)) responses to glucose, 3) steady-state C-peptide and insulin concentrations at plasma glucose of 11.1 mmol/L, and 4) arginine-stimulated maximum C-peptide (ACPR(max)) and insulin (AIR(max)) responses at plasma glucose >25 mmol/L. The fasting C-peptide-to-insulin ratio was used as an estimate of insulin clearance. RESULTS Insulin sensitivity was 46% lower in youth compared with adults (P < 0.001), and youth had greater acute and steady-state C-peptide (2.3- and 1.3-fold, respectively; each P < 0.001) and insulin responses to glucose (AIR(g) 3.0-fold and steady state 2.2-fold; each P < 0.001). Arginine-stimulated C-peptide and insulin responses were also greater in youth (1.6- and 1.7-fold, respectively; each P < 0.001). After adjustment for insulin sensitivity, all-cell responses remained significantly greater in youth. Insulin clearance was reduced in youth (P < 0.001). Participants with diabetes had greater insulin sensitivity (P = 0.026), with lesser C-peptide and insulin responses than those with IGT (all P < 0.001) but similar insulin clearance (P = 0.109). CONCLUSIONS In people with IGT or recently diagnosed diabetes, youth have lower insulin sensitivity, hyperresponsive-cells, and reduced insulin clearance compared with adults. Whether these age-related differences contribute to declining-cell function and/or impact responses to glucose-lowering interventions remains to be determined.
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