Elbein S C
Division of Endocrinology and Metabolism, Veterans Affairs Medical Center and University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
J Nutr. 1997 Sep;127(9):1891S-1896S. doi: 10.1093/jn/127.9.1891S.
Familial aggregation and concordance in monozygotic and dizygotic twins argue strongly for a genetic etiology to noninsulin-dependent diabetes (NIDDM). Nonetheless, studies of pathways implicated by the known physiology have failed to identify gene defects that can explain the genetic susceptibility. In contrast, studies of early onset dominant diabetes have revealed three major loci resulting in diminished insulin secretion. Recently, studies have taken a new approach to map the genes causing typical NIDDM using large numbers of families or sibling pairs. The first reports of these studies have suggested possible loci on chromosomes 1, 2 and 12, but no report has been confirmed. Other studies have examined the quantitative defects that may be precursors of clinical NIDDM such as hyperinsulinemia, hyperglycemia, insulin response to glucose and obesity. These studies have suggested additional loci that may contribute to NIDDM susceptibility, but the genes responsible for most of these loci remain unknown. Studies of NIDDM susceptibility and the role of obesity genes in that susceptibility have entered an exciting new phase, but the challenges of complex disease genetics in humans will have to be conquered to translate this research into preventive or therapeutic benefits.
单卵双生子和双卵双生子中的家族聚集性及一致性有力地表明非胰岛素依赖型糖尿病（NIDDM）具有遗传病因。尽管如此，对已知生理学所涉及途径的研究未能确定可解释遗传易感性的基因缺陷。相比之下，对早发性显性糖尿病的研究已揭示出三个导致胰岛素分泌减少的主要基因座。最近，研究采用了一种新方法，利用大量家庭或同胞对来定位导致典型NIDDM的基因。这些研究的首批报告提示了1号、2号和12号染色体上可能存在的基因座，但尚无报告得到证实。其他研究则考察了可能是临床NIDDM先兆的定量缺陷，如高胰岛素血症、高血糖症、胰岛素对葡萄糖的反应及肥胖症。这些研究提示了其他可能与NIDDM易感性相关的基因座，但大多数这些基因座的相关基因仍不清楚。对NIDDM易感性及肥胖基因在该易感性中作用的研究已进入一个令人兴奋的新阶段，但要将这项研究转化为预防或治疗效益，还必须克服人类复杂疾病遗传学方面的挑战。
