Introduction: Atypical Low BMI Diabetes Mellitus (ALBDM) constitutes an unclassified form of diabetes that is likely to be prevalent in low- and middle-income countries. Recently, we reported in Diabetes Care that such individuals demonstrate striking defects in insulin secretion, despite absence of visible pancreatic pathology (PMID: 35522035). This study aims to determine whether defects in the incretin axis might contribute to impaired insulin secretion in ALBDM.

Methodology: We assessed the glucagon and incretin (GLP-1, GIP, and Oxyntomodulin) responses to an oral glucose tolerance test (OGTT) in patients with ALBDM. Ten male subjects demonstrating features of ALBDM (n=10, age 33±8.3 years, BMI 18.5±1.1 kg/m2, HbA1c 7.5±0.7%) were compared with 7 healthy BMI-matched normoglycemic (HbA1c: 5.0±0.3%) controls. All subjects underwent an OGTT, with blood sampling for C-peptide and incretin levels at nine specific time points. Insulin secretion rate (ISR) was calculated by C-peptide deconvolution using ISEC software, and total secretion rate for incretins were calculated as area under the curve (AUC) using the Trapezoid method with linear interpolation.

Results: As we previously reported, ALBDM subjects displayed impaired insulin secretion (50% reduction in post-OGTT insulin AUC, p=0.007). There was a profound reduction of OGTT-stimulated rise in the incretins GLP-1 (80% reduction; p=0.055), GIP (79% reduction; p=0.02) and oxyntomodulin (75% reduction; p=0.007) in ALBDM subjects compared to controls. In ALBDM subjects, mild hyperglucagonemia was observed in the early postprandial phase at 15 min of the OGTT followed by slow postprandial suppression.

Conclusions: Significant reductions in levels of GLP-1, GIP and Oxyntomodulin and an accompanying early phase of hyperglucagonemia suggest potential defects in development and/or function of enteroendocrine cells, which may contribute to defective insulin secretion and hyperglycemia in patients with Atypical Low BMI Diabetes Mellitus.


F.Jebasingh: None. N.Jiang: None. M.Hawkins: None. N.Thomas: None. S.Anoop: None. M.E.Kurian: None. V.N.Sandeep: None. F.Christina: None. S.Jennifer: None. A.Jose: None. P.Christudoss: None. G.Rebekah: None.


Endocrine Society of India

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at