The aim of the current study was to characterize β-cell function, insulin sensitivity and line of inheritance in patients with recent-onset type 2 diabetes of Yemenite and non-Yemenite Jewish origin.
A cohort study including 121 GAD negative diabetic patients, 59 of Yemenite and 62 of non-Yemenite origin, treated by diet ± oral antihyperglycemic monotherapy who underwent 180-min meal tolerance test (MMT). Based on MMT, indexes of insulin resistance and secretion were calculated.
There were no significant differences in age, sex, diabetes duration, BMI, HbA1c and lipid profile. A significant difference was found in family history of diabetes: 63 % of patients of Yemenite origin had maternal inheritance versus 35 % in the non-Yemenite origin (p < 0.001). Both indexes of β-cell function, the insulinogenic and the disposition indexes were significantly lower in patients of Yemenite origin compared with non-Yemenite origin (0.66 ± 0.4 vs. 0.93 ± 0.8, p = 0.04; 2.3 ± 1.8 vs. 3.3 ± 3.3, p = 0.04, respectively) with no difference in insulin sensitivity. When females and males were analyzed separately, the difference in maternal inheritance remained significant in both, but the difference in β-cell function indexes was observed only in males (p = 0.03, p = 0.01, respectively).
Males with recent-onset diabetes of Yemenite origin have a significant reduction of β-cell function and reduced ability to compensate for insulin resistance compared with diabetic males of non-Yemenite origin. Both males and females of Yemenite origin have a significantly higher maternal inheritance of diabetes. These data suggest different underlying mechanisms leading to early loss of β-cell in diabetic males of Yemenite origin.
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Area under the curve
Body mass index
Glutamic acid decarboxylase
Homeostasis model assessment
Meal tolerance test
Non-Yemenite diabetes mellitus
Yemenite diabetes mellitus
Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L (2014) The many faces of diabetes: a disease with increasing heterogeneity. Lancet 383:1084–1094
Meier JJ, Bonadonna RC (2013) Role of reduced β-cell mass versus impaired β-cell function in the pathogenesis of type 2 diabetes. Diabetes Care 36:S113–119
Halban PA, Polonsky KS, Bowden DW, Hawkins MA, Ling C, Mather KJ et al (2014) β-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. Diabetes Care 37:1751–1758
Federici M, Hribal M, Perego L, Ranalli M, Caradonna Z, Perego C (2001) High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program. Diabetes 50:1290–1301
Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110
Folli F, Okada T, Perego C, Gunton J, Liew CW, Akiyama M et al (2011) Altered insulin receptor signaling and β-cell cycle dynamics in type 2 diabetes mellitus. PLoS ONE 6:e28050
Guardado-Mendoza R, Davalli AM, Chavez AO, Hubbard GB, Dick EJ, Mailuf-Cruz A et al (2009) Pancreatic islet amyloidosis, β-cell apoptosis, and α- cell proliferation are determinants of islet remodeling in type-2 diabetic baboons. PNAS 106:13992–13997
Sobngwi E, Boudou P, Mauvais-Jarvis F, Leblanc H, Velho G, Vexiau P et al (2003) Effect of a diabetic environment in utero on predisposition to type 2 diabetes. Lancet 361:1861–1865
Gautier JF, Wilson C, Weyer C, Mott D, Knowler WC, Cavaghan M et al (2001) Low acute insulin secretory responses in adult offspring of people with early onset type 2 diabetes. Diabetes 50:1828–1833
Cohen AM, Marom L (1993) Diabetes and accompanying obesity, hypertension and ECG abnormalities in Yemenite Jews 40 years after immigration to Israel. Diabetes Res 23:65–74
Weingarten MA, Katzir I, Sprecher E, Kobzantsev S, Zelzer C, Kahan E (2000) Diabetes and ischemic heart disease among Yemenite immigrants in Israel. Isr Med Assoc J 2:207–210
Matsuda M, De Fronzo RA (1999) Insulin sensitivity indices obtained from glucose tolerance testing: comparison with euglycemic insulin clamp. Diabetes Care 22:1462–1470
Selimoglu H, Duran C, Kiyici S, Guclu M, Ersoy C, Ozkaya G et al (2009) Comparison of composite whole body insulin sensitivity index derived from mixed meal test and oral glucose tolerance test in insulin resistant obese subjects. Endocrine 36:299–304
Bache F, Gungor N, Lee S, de las Heras J, Arslanian S (2013) Indices of insulin secretion during a liquid mixed-meal test in obese youth with diabetes. J Pediatr 162:924–929
Maki KC, McKenney JM, Farmer MV, Reeves MS, Dicklin MR (2009) Indices of insulin sensitivity and secretion from a standard liquid meal test in subjects with type 2 diabetes, impaired or normal fasting glucose. Nutr J 8:22. doi:10.1186/1475-2891-8-22
Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ et al (2009) Oral disposition index predicts development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care 32:335–341
Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW et al (1993) Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for a hyperbolic function. Diabetes 42:1663–1672
Ram J, Snehalatha C, Selvam S, Nanditha A, Shetty AS, Godsland IF, Johnston DG, Ramachandran A (2015) The oral disposition index is a strong predictor of incident diabetes in Asian Indian prediabetic men. Acta Diabetol 52:733–741
Blaychfeld-Magnazi M, Reshef N, Zornitzki T, Knobler H (2010) The prevalence and severity of hypertension in patients with type 2 diabetes of Yemenite origin is lower than in non-Yemenite diabetics. Diabetologia 53:S556
Facchini FS, Hollenbeck CB, Jeppersen J, Chen YD, Reaven GM (1992) Insulin resistance and cigarette smoking. Lancet 339:1128–1130
Fetita LS, Sobngwi E, Serradas P, Calvo F, Gautier JF (2006) Consequences of fetal exposure to maternal diabetes in offspring. J Clin Endocrin Metab 91:3718–3724
Alcolado JC, Alcolado R (1991) Importance of maternal history of non-insulin dependent diabetic patients. BMJ 302:1178–1180
Thomas F, Balkau B, Vauzelle-Kervroedan F, Papoz L (1994) Maternal effect and familial aggregation in NIDDM. Diabetes 43:63–67
Meigs JB, Cupples LA, Wilson PW (2000) Parental transmission of type 2 diabetes: the Framingham offspring study. Diabetes 49:2201–2207
Maassen JA, T Hart LM, Van Essen E, Heine RJ, Nijpels G, Jahangir Tafrechi RS RS et al (2004) Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes 53:S103–109
Pettitt DJ, Aleck KA, Baird HR, Carraher MJ, Bennett PH, Knowler WC (1988) Congenital susceptibility to NIDDM. Diabetes 37:622–628
Mauvais-Jarvis F, Sobngwi E, Porcher FI (2004) Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance. Diabetes 53:645–653
Piñero-Piloña A, Litonjua P, Aviles-Santa L, Raskin P (2001) Idiopathic type 1 diabetes in Dallas, Texas: a 5-year experience. Diabetes Care 24:1014–1018
Godsland IF (2005) Oestrogens and insulin secretion. Diabetologia 48:2213–2220
Liu S, Mauvais-Jarvis F (2010) Minireview: estrogenic protection of beta- cell failure in metabolic diseases. Endocrinology 151:859–864
Tiano JP, Mauvais-Jarvis F (2012) Molecular mechanisms of estrogen receptor suppression of lipogenesis in pancreatic β-cells. Endocrinology 153:2997–3005
The authors wish to thank Dt. Hillary Foot for statistical analysis. This work was supported by a Research Grant from Novo Nordisk and a joint Research Grant from the Institute for Medical Research, Israel–Canada, the Hebrew University, Kaplan Medical Center, and Eelebetamar organization, Israel.
Blaychfeld-Magnazi M. researched data, wrote manuscript, contributed to discussion, reviewed/edited manuscript. Zornitzki T. researched data, wrote manuscript, contributed to discussion, reviewed/edited manuscript. Ulman M. researched data, contributed to discussion. Madar Z. researched data, contributed to discussion, reviewed/edited manuscript. Knobler H. researched data, wrote manuscript, contributed to discussion, reviewed/edited manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
The study has been reviewed by an institutional review board, and has been performed in accordance with ethical standards laid down in an appropriate version of the 1964 of the Helsinki declaration.
Human and animal rights
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).
Informed consent was obtained from all patients for being included in the study.
Managed by Massimo Federici.
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Blaychfeld-Magnazi, M., Zornitzki, T., Ulman, M. et al. Early beta-cell dysfunction characterizes males with type 2 diabetes of Yemenite origin. Acta Diabetol 53, 567–574 (2016). https://doi.org/10.1007/s00592-016-0838-0
- β-cell function
- Maternal inheritance
- Insulin secretion