No abstract

Resistance to insulin-mediated glucose disposal is a common finding in patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as in nondiabetic individuals with hypertension. In an effort to identify the generic loci responsible for variations in blood pressure in individuals at increased risk of insulin resistance, we studied the distribution of blood pressure in 48 Taiwanese families with NIDDM and conducted quantitative sib-pair linkage analysis with candidate loci for insulin resistance, lipid metabolism, and blood pressure control. We found no evidence for linkage of the angiotensin converting enzyme locus on chromosome 17, nor the angiotensinogen and renin loci on chromosome 1, with either systolic or diastolic blood pressures. In contrast, we obtained significant evidence for linkage of systolic blood pressure, but not diastolic blood pressure, to a genetic region at or near the lipoprotein lipase (LPL) locus on the short arm of chromosome 8 ( P ‫؍‬ 0.002, n ‫؍‬ 125 sib-pairs, for the haplotype generated from two simple sequence repeat markers within the LPL gene). Further strengthening this linkage observation, two flanking marker loci for LPL locus, D8S261 (9 cM telomeric to LPL locus) and D8S282 (3 cM centromeric to LPL locus), also showed evidence for linkage with systolic blood pressure ( P ϭ 0.02 and 0.0002 for D8S261 and D8S282, respectively). Two additional centromeric markers (D8S133, 5 cM from LPL locus, and NEFL, 11 cM from LPL locus) yielded significant P values of 0.01 and 0.001, respectively. Allelic variation around the LPL gene locus accounted for as much as 52-73% of the total interindividual variation in systolic blood pressure levels in this data set. Thus, we have identified a genetic locus at or near the LPL gene locus which contributes to the variation of systolic blood pressure levels in nondiabetic family members at high risk for insulin resistance and NIDDM. ( J.Clin. Invest. 1996. 97:2111-2118.)

This study was initiated to reevaluate the changes in basal hepatic glucose production (HGP) rate that occur in patients with non-insulin-dependent diabetes mellitus (NIDDM). Measurements were made in 51 volunteers: 18 with normal glucose tolerance and 33 with newly diagnosed NIDDM of varying degrees of severity. To avoid the methodological problems associated with quantifying HGP over short time periods, using non-steady-state isotopic kinetics, radiolabeled glucose was infused for a 12-h period, from 10 P.M. to 10 A.M. with HGP quantified from 9 to 10 A.M.. The results showed that fasting plasma glucose (FPG) concentration and HGP were significantly correlated (r = 0.68, P < 0.001) in patients with NIDDM. However, when the 33 patients with NIDDM were divided into three groups of 11 each on the basis of FPG concentration, it became clear that the relationship between FPG and HGP was complex. Thus, values for HGP in patients with NIDDM and FPG < 180 mg/dl were not higher than in the normal population (1.67 +/- 0.07 vs. 1.69 +/- 0.04 mg.kg-1.min-1, NS). Significant increases (P < 0.01) in HGP above normal were seen in the 11 patients with NIDDM and FPG concentrations between 180 and 250 mg/dl (2.05 +/- 0.07 mg.kg-1.min-1), as well as in those with FPG > 250 mg/dl (2.18 +/- 0.13 mg.kg-1.min-1). Although those with the highest FPG concentrations tended to have the greatest values for HGP, the difference between the latter two groups of patients with NIDDM was not statistically significant. Finally, HGP rates in the 11 patients with FPG concentrations > 250 mg/dl were only 29% higher than values in the control population.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma glucose and insulin responses to a 75-g oral glucose load, and the steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations after an infusion of somatostatin, insulin, and glucose, were determined 2 months after delivery in 26 women; 13 who had a normal pregnancy and 13 who developed preeclampsia. The plasma glucose response to oral glucose was not different in the two groups, but the plasma insulin response was significantly greater (P < .02) in those who had been preeclamptic. Although the mean (+/- SE) SSPI concentrations during the infusion study were similar in the two groups (51 +/- 2 v 56 +/- 2 microU/mL), the SSPG concentrations were significantly higher (P < .02) in those who developed preeclampsia (160 +/- 17 v 119 +/- 17 mg/dL). Thus, when studied 2 months after delivery, women who developed preeclampsia were relatively insulin resistant and hyperinsulinemic when compared to those who had an uncomplicated pregnancy.