Clinical Investigation

Kidney International (1993) 44, 139–146; doi:10.1038/ki.1993.224

Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes

Romano Nosadini, Maria Sambataro, Karl Thomaseth, Giovanni Pacini, Maria Rita Cipollina, Enrico Brocco, Anna Solini, Andrea Carraro, Mario Velussi, Francesco Frigato and Gaetano Crepaldi

Department of Internal Medicine, University of Padova, Padova; Diabetic Outpatient's Clinic of Monfalcone and Mestre, Monfalcone and Mestre; and Institute of Systems Science & Biomedical Engineering, LADSEB-CNR, Padova, Italy

Correspondence: R Nosadini, Istituto di Medicina Interna, Patologia Medica Ia, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy.

Received 5 October 1992; Revised 25 February 1993; Accepted 25 February 1993.

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Abstract

Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes. Sodium retention has been advocated to give rise to hypertension in humans. Increases in blood glucose and insulin concentrations ensue in the stimulation of sodium reabsorption by the kidney. Although the combined occurrence of hyperglycemia and hyperinsulinemia, frequently secondary to insulin resistance with regard to carbohydrate metabolism, is a hallmark of non-insulin dependent diabetes (NIDDM), the role of these abnormalities in determining an impaired natriuresis in NIDDM is not yet fully understood. We studied sodium homeostasis in 14 control subjects and 59 NIDDM normotensive, normoalbuminuric patients who were divided into two groups with markedly impaired (Group 2 NIDDM: 30) and less severely impaired (Group 1 NIDDM: 29) insulin sensitivity during euglycemic-hyperinsulinemic (80 to 90 microU/ml plasma insulin) clamp. A hyperglycemic (9 mmol/liter plasma glucose)—nearly euinsulinemic (20 to 40 microU/ml plasma insulin) clamp was also performed in the same 14 controls and in two cohorts of 22 Group 2 and 17 Group 1 NIDDM patients. The two groups of patients had similar overnight fasting glucose levels (Group 1 NIDDM vs. Group 2 NIDDM: 176 plusminus 13 vs. 185 plusminus 15 mg/dl, mean plusminus SE). Conversely, overnight fasting plasma insulin was significantly higher in Group 2 NIDDM than in Group 1 NIDDM patients (Group 1 NIDDM vs. Group 2 NIDDM: 12 plusminus 3 vs. 18 plusminus 3 microU/ml, P < 0.05). Both NIDDM Groups had higher plasma glucose and insulin than controls (75 plusminus 4 mg/dl and 6 plusminus 3 microU/ml). Blood pressure levels and albumin excretion rates were slightly but significantly higher in Group 2 NIDDM, but not in Group 1 NIDDM patients, than in controls. Insulin administration during the euglycemic-hyperinsulinemic clamp decreased in a similar manner the sodium excretion rate in controls and in both NIDDM groups. Conversely, the sodium excretion rate was always significantly lower in Group 2 than in Group 1 NIDDM patients and in controls during the hyperglycemic, near euinsulinemic clamp (euglycemia and hyperglycemia; Controls vs. Group 1 vs. Group 2: 156 plusminus 14 and 123 plusminus 15 vs. 138 plusminus 17 and 111 plusminus 10, NS; vs. 101 plusminus 8 and 74 plusminus 9, P < 0.01 vs. both, micromol dot min-1 dot 1.73 m-2). The sodium excretion rate was lower during hyperglycemia than euglycemia both in controls and NIDDM patients. An inverse relationship was observed between daily sodium excretion rate and glucose filtered load in both Group 1 and Group 2 NIDDM patients, at least up to a glucose filtered load of 220 mg dot min-1 dot 1.73 m-2. The daily sodium excretion rate was significantly lower in Group 2 than in Group 1 NIDDM patients, despite similar circulating glucose levels and rates of glucose filtered load. We conclude that excessive, glucose-bound, renal sodium reabsorption occurs in all normotensive, normoalbuminuric NIDDM patients, but that sodium retention is markedly increased in patients with severe insulin resistance, despite similar circulating levels of glucose and insulin.

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