PMID- 12017222 OWN - NLM STAT- MEDLINE DCOM- 20021112 LR - 20221207 IS - 0334-018X (Print) IS - 0334-018X (Linking) VI - 15 Suppl 1 DP - 2002 Apr TI - Impaired beta-cell and alpha-cell function in African-American children with type 2 diabetes mellitus--"Flatbush diabetes". PG - 493-501 AB - The incidence of type 2 diabetes mellitus (T2DM) in children and adolescents has substantially increased over the past decade. This is attributed to obesity, insulin resistance and deficient beta-cell function. In children a pubertal increase in insulin resistance and an inability to mount an adequate beta-cell insulin response results in hyperglycemia. Adults with T2DM have a diminished first phase response to intravenous glucose and a delayed early insulin response to oral glucose. Long-term studies show progressive loss of beta-cell function in T2DM in adults; however, such long-term studies are not available in children. To characterize beta- and alpha-cell function in African-American adolescents with established T2DM, we used mixed meal, intravenous glucagon and oral glucose tolerance testing and compared them to obese non-diabetic controls. T2DM was defined as fasting C-peptide >0.232 nmol/l and absent autoimmune markers. BETA-CELL FUNCTION: Meal testing in 24 children and adolescents with T2DM, mean age 14 years, BMI 30 kg/m2, Tanner stage II-V, HbA1c 8.9%, were compared with BMI- and age-matched controls. Forty percent presented with DKA. Half were treated with insulin and half with diet/oral anti-diabetic agents. Although absolute C-peptide response in both groups was similar, the incremental rise in C-peptide relative to plasma glucose in the patients with T2DM compared to controls was 40% and 35% lower 30 and 60 min after the meal, p <0.007 and p <0.026. Glucagon testing in 20 pediatric patients with T2DM compared with 15 matched controls showed significantly lower 6 min stimulated C-peptide relative to the ambient plasma glucose in patients with T2DM compared to controls (0.039 +/- 0.026 vs 0.062 +/- 0.033, p <0.05). The clinical utility is that 78% of patients with a 6 min C-peptide <1.4 nmol required insulin, while 81% of those >1.4 nmol required oral anti-diabetic agents, p <0.0001. Furthermore, the duration of T2DM up to 5 years after diagnosis was associated with lower fasting and glucagon-stimulated C-peptide levels, implying worsening beta-cell function over time, even in children and adolescents. ALPHA-CELL FUNCTION: During meal testing, children and adolescents with T2DM had less suppression of plasma glucagon than non-diabetic controls; this was more severe with longer duration of T2DM and poorer glycemic control. BETA-CELL RECOVERY: In African-American and Hispanic adults, intensive treatment of blood glucose may achieve beta-cell recovery with 35-40% of newly diagnosed patients going into remission after 6 months treatment. They remain off anti-diabetic pharmacological agents in remission for a median of over 3 years with normal HbA1c levels. We hypothesize this to be due to removal of a critical component of glucose or lipotoxicity at the level of the beta-cell and/or peripheral tissue. Four of 20 African-American children presenting with mean glucose 650 mg/dl maintained normal HbA1c levels on small doses of metformin after initial treatment with multiple insulin injections with or without metformin. This suggests a marked recovery of beta-cell function, similar to that in adults. SUMMARY: T2DM in children, as in adults, is characterized by insulin deficiency relative to insulin resistance. Plasma C-peptide levels may be clinically useful in guiding therapeutic choices, since patients with lower levels required insulin treatment; beta-cell function is also diminished with longer duration of T2DM. The possibility exists that in children, as in adults, intensive glycemic regulation may allow for beta-cell recovery and preservation. Thus, optimum beta- and alpha-cell function are central to the prevention of DM and maintenance of good glycemic control in African-American and Hispanic children and adolescents with T2DM. FAU - Banerji, Mary Ann AU - Banerji MA AD - Department of Internal Medicine, State University of New York Health Sciences Center at Brooklyn, 11203, USA. mbanerji@downstate.edu LA - eng PT - Journal Article PT - Review PL - Germany TA - J Pediatr Endocrinol Metab JT - Journal of pediatric endocrinology & metabolism : JPEM JID - 9508900 RN - 0 (C-Peptide) RN - 0 (Insulin) RN - 9007-92-5 (Glucagon) SB - IM MH - Adolescent MH - Adult MH - *Black People MH - Body Mass Index MH - C-Peptide/blood MH - Child MH - Diabetes Mellitus, Type 2/drug therapy/*physiopathology MH - Food MH - Glucagon MH - Glucose Intolerance/physiopathology MH - Glucose Tolerance Test MH - Humans MH - Insulin/metabolism MH - Insulin Resistance MH - Insulin Secretion MH - Islets of Langerhans/*physiopathology MH - Puberty RF - 53 EDAT- 2002/05/23 10:00 MHDA- 2002/11/26 04:00 CRDT- 2002/05/23 10:00 PHST- 2002/05/23 10:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/05/23 10:00 [entrez] PST - ppublish SO - J Pediatr Endocrinol Metab. 2002 Apr;15 Suppl 1:493-501.