Ghrelin is a novel peptide that acts on the growth hormone (GH) secretagogue receptor in the pituitary and hypothalamus. It may function as a third physiological regulator of GH secretion, along with GH-releasing hormone and somatostatin. In addition to the action of ghrelin on the GH axis, it appears to have a role in the determination of energy homeostasis. Although feeding suppresses ghrelin production and fasting stimulates ghrelin release, the underlying mechanisms controlling this process remain unclear. The purpose of this study was to test the hypotheses, by use of a stepped hyperinsulinemic eu-hypo-hyperglycemic glucose clamp, that either hyperinsulinemia or hypoglycemia may influence ghrelin production. Having been stable in the period before the clamp, ghrelin levels rapidly fell in response to insulin infusion during euglycemia (baseline ghrelin 207 Ϯ 12 vs. 169 Ϯ 10 fmol/ml at t ϭ 30 min, P Ͻ 0.001). Ghrelin remained suppressed during subsequent periods of hypoglycemia (mean glucose 53 Ϯ 2 mg/dl) and hyperglycemia (mean glucose 163 Ϯ 6 mg/dl). Despite suppression of ghrelin, GH showed a significant rise during hypoglycemia (baseline 4.1 Ϯ 1.3 vs. 28.2 Ϯ 3.9 g/l at t ϭ 120 min, P Ͻ 0.001). Our data suggest that insulin may suppress circulating ghrelin independently of glucose, although glucose may have an additional effect. We conclude that the GH response seen during hypoglycemia is not regulated by circulating ghrelin. growth hormone; somatostatin; hypothalamus; hypoglycemia; glucose clamp GHRELIN IS A NOVEL PEPTIDE that acts on the growth hormone (GH) secretagogue receptor in the pituitary and hypothalamus, possibly functioning as a third physiological regulator of GH secretion along with GHreleasing hormone (GHRH) and somatostatin. In addition to the action of ghrelin on the GH axis, it appears to have a role in the determination of energy homeostasis (3, 12, 13). Ghrelin acts as an orexigenic hormone, stimulating both neuropeptide Y (NPY) and agoutirelated peptide, and thus feeding (14, 21). Although feeding suppresses ghrelin production and fasting stimulates ghrelin release, the underlying mechanisms controlling these processes remain unclear (4,19). This relationship is the opposite of that seen with leptin (14), which has been shown to be increased by insulin (18). Specifically, the roles that alterations in plasma glucose and insulin have in regulating ghrelin secretion have not been established. To address this issue, we employed a stepped hyperinsulinemic eu-hypo-hyperglycemic glucose clamp. This procedure allowed us to examine the ghrelin response to marked variations in circulating concentrations of insulin and glucose in human subjects. METHODSEleven young adult volunteers (9 women, 2 men) participated in the study. The age of the subjects was 24 Ϯ 4 yr (range 18-31 yr), and the body mass index was 22.1 Ϯ 2.8 kg/m 2 (18.4-26.6 kg/m 2 ). All subjects were healthy and taking no medication. They were instructed to maintain their normal physical activity and to consume a normal diet contai...

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OBJECTIVETo assess the safety and efficacy of dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes.RESEARCH DESIGN AND METHODSWe treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment.RESULTSIn the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% (P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring (CGM) of 148.8 mg/dL (8.3 mmol/L) (P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) (P = 0.002) in HbA1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3 mg/dL (9.5 mmol/L), and a decrease of 0.06% (0.65 mmol/mol) in HbA1c. The percentage of time in target glucose range 70–180 mg/dL (3.9–10.0 mmol/L) increased from baseline with sotagliflozin compared with placebo, to 68.2% vs. 54.0% (P = 0.003), while the percentage of time in hyperglycemic range >180 mg/dL (10.0 mmol/L) decreased from baseline, to 25.0% vs. 40.2% (P = 0.002), for sotagliflozin and placebo, respectively. Body weight decreased (1.7 kg) with sotagliflozin compared with a 0.5 kg gain (P = 0.005) in the placebo group.CONCLUSIONSAs adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes.

This study explored the incorporation of type 1 diabetes mellitus (T1DM) into self-identity among adolescents. Guided interviews explored 40 adolescents' views of T1DM in relation to their sense of self and relationships with others. Responses were analyzed using thematic analysis. Results revealed that the entire sample described T1DM as a significant burden; many described how T1DM made them feel less "normal." Adolescents described both positive and negative aspects of self-management in social relationships, though most reported benefits in sharing T1DM with friends. Females were more likely to share information about T1DM and to describe positive changes in self-perception as a result of T1DM. The psychosocial processes related to integration of T1DM into self-identity described in these qualitative data provide hypothesis-generating findings that can guide future quantitative research examining incorporation of T1DM into adolescent self-identity in relation to measures of self-esteem, peer orientation, self-management, and glycemic control.

Adolescents with PCOS treated with metformin or OCP experienced similar beneficial outcomes including reduction in androgen levels, weight loss, and increased insulin sensitivity. The choice of a treatment agent for long-term use will depend on safety profiles, therapeutic goals and patient adherence.

OBJECTIVEExenatide improves postprandial glycemic excursions in type 2 diabetes. Exenatide could benefit type 1 diabetes as well. We aimed to determine an effective and safe glucose-lowering adjuvant exenatide dose in adolescents with type 1 diabetes.RESEARCH DESIGN AND METHODSEight subjects completed a three-part double-blinded randomized controlled study of premeal exenatide. Two doses of exenatide (1.25 and 2.5 μg) were compared with insulin monotherapy. Prandial insulin dose was reduced by 20%. Gastric emptying and hormones were analyzed for 300 min postmeal.RESULTSTreatment with both doses of exenatide versus insulin monotherapy significantly reduced glucose excursions over 300 min (P < 0.0001). Exenatide administration failed to suppress glucagon but delayed gastric emptying (P < 0.004).CONCLUSIONSAdjunctive exenatide therapy reduces postprandial hyperglycemia in adolescents with type 1 diabetes. This reduction in glucose excursion occurs despite reduction in insulin dose. We suggest that exenatide has therapeutic potential as adjunctive therapy in type 1 diabetes.

Literacy and numerical skills of caregivers significantly influence glycemic control of their children with type 1 diabetes. Assessing literacy/numeracy skills of caregivers and addressing these deficiencies may be crucial in optimizing glycemic control.

Postprandial hyperglycemia and preprandial hypoglycemia contribute to poor glycemic control in type 1 diabetes. We hypothesized that postprandial glycemic excursions could be normalized in type 1 diabetes by suppressing glucagon with pramlintide acetate in the immediate postprandial period and supplementing glucagon in the late postprandial period. A total of 11 control subjects were compared with 8 type 1 diabetic subjects on insulin pump therapy, using the usual insulin bolus-to-carbohydrate ratio during a standard liquid meal. Type 1 diabetic subjects were then randomized to two open-labeled studies. On one occasion, type 1 diabetic subjects received a 60% increase in the insulin bolus-to-carbohydrate ratio with minidose glucagon rescue injections, and on the other occasion type 1 diabetic subjects received 30 -45 g pramlintide with their usual insulin bolus-to-carbohydrate ratio. Glucose, glucagon, amylin (pramlintide), and insulin concentrations were measured for 420 min. The plasma glucose area under the curve (AUC) for 0 -420 min was lower in control versus type 1 diabetic subjects (316 ؎ 5 vs. 929 ؎ 18 mg ⅐ h ؊1 ⅐ dl ؊1 , P < 0.0001). Pramlintide, but not an increase in insulin, reduced immediate postprandial hyperglycemia (AUC 0 -180 min 470 ؎ 43 vs. 434 ؎ 48 mg ⅐ h ؊1 ⅐ dl ؊1 , P < 0.01). Pramlintide administration suppressed glucagon (P < 0.02), and glucagon injections prevented late hypoglycemia with increased insulin. In summary, in type 1 diabetes, glucagon modulation with pramlintide as an adjunct to insulin therapy may prove beneficial in controlling postmeal glycemic swings.