Insulin resistance may be a mechanism linking non-insulin-dependent diabetes mellitus (NIDDM) to hypertension and cardiovascular mortality. Microalbuminuria also is an independent risk factor of cardiovascular mortality and of hypertension. Little information is available in the literature on the relationship between microalbuminuria and insulin action. This study investigated the relationships between blood pressure (BP) levels, microalbuminuria, and insulin resistance in NIDDM patients. Seventy-five NIDDM patients attending the outpatient clinic of the Department of Internal Medicine of the University Hospital in Padua, Italy participated in the cross-sectional part of our study. These subjects were divided into four groups on the basis of BP levels and albumin excretion rate (AER): 28 normotensive normoalbuminuric (NIDDMS1), 19 hypertensive normoalbuminuric (NIDDM2), 15 normotensive microalbuminuric (NIDDM3), and 13 hypertensive microalbuminuric patients (NIDDM4). We defined microalbuminuria as an AER > 20 μg/min. Patients with BP levels > 145/90 mmHg were considered hypertensive. A group of 20 normal subjects served as control subjects. The results from the cross-sectional study indicate that the mean of insulin-induced whole-body glucose utilization, primarily an index of extrahepatic insulin action, was lower at all insulin infusion steps in the group of hypertensive and/or microalbuminuric patients than in the group of normotensive normoalbuminuric patients and control subjects. Hepatic glucose output, an index of insulin action in the liver, was on average less efficiently inhibited in all of the patients than in the control subjects, regardless of the BP levels or the AER. The 28 normotensive normoalbuminuric patients belonging to NIDDM1 had extrahepatic insulin sensitivity patterns that were not significantly different on average from those of control subjects, although broadly dispersed in a wide range. Thus these patients were divided in two cohorts with normal (cohort B; n = 14) and impaired (cohort A; n = 14) extrahepatic insulin sensitivity and provided the data for our six-year follow-up program. During the follow-up study of these normotensive normoalbuminuric patients (cohort A), diabetic individuals more frequently developed hypertension (50 vs. 0%, P < 0.01) and microalbuminuria (43 vs. 14%, P < 0.01) than did cohort B diabetic patients. These results support the conclusions that, in NIDDM, 1) insulin-induced glucose uptake value by extrahepatic tissues is on average normal in the group of patients with normal BP levels and normal AER, whereas it is on average impaired in the group of subjects with hypertension or microalbuminuria or both; 2) insulin sensitivity in hepatic tissue is reduced on average in the overall population of NIDDM patients, regardless of the presence of hypertension or microalbuminuria or both; and 3) insulin resistance in extrahepatic tissues seems to precede the onset of hypertension and microalbuminuria.
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March 01 1994
Impaired Insulin-Induced Glucose Uptake by Extrahepatic Tissue Is Hallmark of NIDDM Patients Who Have or Will Develop Hypertension and Microalbuminuria
Romano Nosadini;
Romano Nosadini
Department of Internal Medicine, the University Hospital
Padua
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Anna Solini;
Anna Solini
Department of Internal Medicine, the University Hospital
Padua
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Mario Velussi;
Mario Velussi
Diabetic Clinic of Monfalcone
Gorizia
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Bruno Muollo;
Bruno Muollo
Diabetic Clinic of Este
Padua, Italy
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Francesco Frigato;
Francesco Frigato
Diabetic Clinic of Mestre
Venice
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Maria Sambataro;
Maria Sambataro
Department of Internal Medicine, the University Hospital
Padua
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Maria Rita Cipollina;
Maria Rita Cipollina
Department of Internal Medicine, the University Hospital
Padua
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Fausto Riva De;
Fausto Riva De
Department of Internal Medicine, the University Hospital
Padua
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Enrico Brocco;
Enrico Brocco
Department of Internal Medicine, the University Hospital
Padua
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Gaetano Crepaldi
Gaetano Crepaldi
Diabetic Clinic of Mestre
Venice
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Address correspondence and reprint requests to Dr. Romano Nosadini, Istituto di Medicina Interna, Patologia Medica I, Policlinico Universitario, Via Giustiniani 2, 35128 Padua, Italy.
Diabetes 1994;43(3):491–499
Article history
Received:
November 02 1992
Revision Received:
October 13 1993
Accepted:
October 13 1993
PubMed:
8314023
Citation
Romano Nosadini, Anna Solini, Mario Velussi, Bruno Muollo, Francesco Frigato, Maria Sambataro, Maria Rita Cipollina, Fausto Riva De, Enrico Brocco, Gaetano Crepaldi; Impaired Insulin-Induced Glucose Uptake by Extrahepatic Tissue Is Hallmark of NIDDM Patients Who Have or Will Develop Hypertension and Microalbuminuria. Diabetes 1 March 1994; 43 (3): 491–499. https://doi.org/10.2337/diab.43.3.491
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