Insulin resistance is a prominent feature of insulin-dependent diabetes

Ralph A Defronzo, R. Hendler, D. Simonson

Research output: Contribution to journalArticle

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Abstract

Tissue sensitivity to insulin was examined in 36 control subjects and 19 insulin-depenent diabetics with diabetes of long-standing duration (mean = 10 ± 3 yr) employing the insulin clamp technique (Δ plasma insulin concentration ~ 100 μU/ml). Eleven of the diabetics (group I) were studied at their fasting hyperglycemic level (173 mg/dl); the remaining 8 diabetics (group II) were studied after lowering their plasma glucose concentration to euglycemic levels (90 mg/dl). Despite plasma glucose levels that were almost twice as great in the diabetics (group I, 173 versus 91 mg/dl, P < 0.001), insulin-mediated glucose metabolism, 4.77 ± 0.18 mg/kg . min, was reduced by 32% versus controls, 7.03 ± 0.22 mg/kg . min (P < 0.01). When the control subjects were restudied at plasma glucose levels (166 ± 2 mg/dl) that were comparable to those of the diabetics, insulin-mediated glucose metabolism was 12.14 ± 0,96 mg/kg . min (P < 0.01). In diabetics studied at euglycemic levels (group II) insulin-mediated glucose metabolism, 3.39 ± 0.30 mg/kg . min, was reduced even further. The metabolic clearance rate in the 19 diabetics, 3.31 ± 0.23 mg/kg . min, was reduced by 58% compared with controls, 7.83 ± 0.25 (P < 0.001). These results emphasize the severe degree of insulin resistance that exists in the insulin-dependent diabetics. Basal hepatic glucose production in the diabetic group, 2.96 ± 0.24 mg/kg . min, was 26% greater than in the controls, 2.35 ± 0.04 (P < 0.001). The fasting plasma glucose concentration displayed a strong positive correlation (r = 0.857, P < 0.001) with basal hepatic glucose production and was weakly and inversely correlated (r = -0.413, P = 0.07) with the basal glucose clearance. Following hyperinsulinemia, however, suppression of hepatic glucose production was ~ 95% in both diabetics and controls, suggesting that peripheral tissues are primarily responsible for the observed impairment in insulin-mediated glucose uptake. The present results indicate that impaired insulin action is a common feature of insulin-dependent diabetics, despite daily insulin requirements (35 ± 2 U/day) that would not clinically characterize them as being insulin resistant.

Original languageEnglish (US)
Pages (from-to)795-801
Number of pages7
JournalDiabetes
Volume31
Issue number9
StatePublished - 1982
Externally publishedYes

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Insulin Resistance
Insulin
Glucose
Liver
Fasting
Metabolic Clearance Rate
Hyperinsulinism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Insulin resistance is a prominent feature of insulin-dependent diabetes. / Defronzo, Ralph A; Hendler, R.; Simonson, D.

In: Diabetes, Vol. 31, No. 9, 1982, p. 795-801.

Research output: Contribution to journalArticle

Defronzo, RA, Hendler, R & Simonson, D 1982, 'Insulin resistance is a prominent feature of insulin-dependent diabetes', Diabetes, vol. 31, no. 9, pp. 795-801.
Defronzo, Ralph A ; Hendler, R. ; Simonson, D. / Insulin resistance is a prominent feature of insulin-dependent diabetes. In: Diabetes. 1982 ; Vol. 31, No. 9. pp. 795-801.
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abstract = "Tissue sensitivity to insulin was examined in 36 control subjects and 19 insulin-depenent diabetics with diabetes of long-standing duration (mean = 10 ± 3 yr) employing the insulin clamp technique (Δ plasma insulin concentration ~ 100 μU/ml). Eleven of the diabetics (group I) were studied at their fasting hyperglycemic level (173 mg/dl); the remaining 8 diabetics (group II) were studied after lowering their plasma glucose concentration to euglycemic levels (90 mg/dl). Despite plasma glucose levels that were almost twice as great in the diabetics (group I, 173 versus 91 mg/dl, P < 0.001), insulin-mediated glucose metabolism, 4.77 ± 0.18 mg/kg . min, was reduced by 32{\%} versus controls, 7.03 ± 0.22 mg/kg . min (P < 0.01). When the control subjects were restudied at plasma glucose levels (166 ± 2 mg/dl) that were comparable to those of the diabetics, insulin-mediated glucose metabolism was 12.14 ± 0,96 mg/kg . min (P < 0.01). In diabetics studied at euglycemic levels (group II) insulin-mediated glucose metabolism, 3.39 ± 0.30 mg/kg . min, was reduced even further. The metabolic clearance rate in the 19 diabetics, 3.31 ± 0.23 mg/kg . min, was reduced by 58{\%} compared with controls, 7.83 ± 0.25 (P < 0.001). These results emphasize the severe degree of insulin resistance that exists in the insulin-dependent diabetics. Basal hepatic glucose production in the diabetic group, 2.96 ± 0.24 mg/kg . min, was 26{\%} greater than in the controls, 2.35 ± 0.04 (P < 0.001). The fasting plasma glucose concentration displayed a strong positive correlation (r = 0.857, P < 0.001) with basal hepatic glucose production and was weakly and inversely correlated (r = -0.413, P = 0.07) with the basal glucose clearance. Following hyperinsulinemia, however, suppression of hepatic glucose production was ~ 95{\%} in both diabetics and controls, suggesting that peripheral tissues are primarily responsible for the observed impairment in insulin-mediated glucose uptake. The present results indicate that impaired insulin action is a common feature of insulin-dependent diabetics, despite daily insulin requirements (35 ± 2 U/day) that would not clinically characterize them as being insulin resistant.",
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N2 - Tissue sensitivity to insulin was examined in 36 control subjects and 19 insulin-depenent diabetics with diabetes of long-standing duration (mean = 10 ± 3 yr) employing the insulin clamp technique (Δ plasma insulin concentration ~ 100 μU/ml). Eleven of the diabetics (group I) were studied at their fasting hyperglycemic level (173 mg/dl); the remaining 8 diabetics (group II) were studied after lowering their plasma glucose concentration to euglycemic levels (90 mg/dl). Despite plasma glucose levels that were almost twice as great in the diabetics (group I, 173 versus 91 mg/dl, P < 0.001), insulin-mediated glucose metabolism, 4.77 ± 0.18 mg/kg . min, was reduced by 32% versus controls, 7.03 ± 0.22 mg/kg . min (P < 0.01). When the control subjects were restudied at plasma glucose levels (166 ± 2 mg/dl) that were comparable to those of the diabetics, insulin-mediated glucose metabolism was 12.14 ± 0,96 mg/kg . min (P < 0.01). In diabetics studied at euglycemic levels (group II) insulin-mediated glucose metabolism, 3.39 ± 0.30 mg/kg . min, was reduced even further. The metabolic clearance rate in the 19 diabetics, 3.31 ± 0.23 mg/kg . min, was reduced by 58% compared with controls, 7.83 ± 0.25 (P < 0.001). These results emphasize the severe degree of insulin resistance that exists in the insulin-dependent diabetics. Basal hepatic glucose production in the diabetic group, 2.96 ± 0.24 mg/kg . min, was 26% greater than in the controls, 2.35 ± 0.04 (P < 0.001). The fasting plasma glucose concentration displayed a strong positive correlation (r = 0.857, P < 0.001) with basal hepatic glucose production and was weakly and inversely correlated (r = -0.413, P = 0.07) with the basal glucose clearance. Following hyperinsulinemia, however, suppression of hepatic glucose production was ~ 95% in both diabetics and controls, suggesting that peripheral tissues are primarily responsible for the observed impairment in insulin-mediated glucose uptake. The present results indicate that impaired insulin action is a common feature of insulin-dependent diabetics, despite daily insulin requirements (35 ± 2 U/day) that would not clinically characterize them as being insulin resistant.

AB - Tissue sensitivity to insulin was examined in 36 control subjects and 19 insulin-depenent diabetics with diabetes of long-standing duration (mean = 10 ± 3 yr) employing the insulin clamp technique (Δ plasma insulin concentration ~ 100 μU/ml). Eleven of the diabetics (group I) were studied at their fasting hyperglycemic level (173 mg/dl); the remaining 8 diabetics (group II) were studied after lowering their plasma glucose concentration to euglycemic levels (90 mg/dl). Despite plasma glucose levels that were almost twice as great in the diabetics (group I, 173 versus 91 mg/dl, P < 0.001), insulin-mediated glucose metabolism, 4.77 ± 0.18 mg/kg . min, was reduced by 32% versus controls, 7.03 ± 0.22 mg/kg . min (P < 0.01). When the control subjects were restudied at plasma glucose levels (166 ± 2 mg/dl) that were comparable to those of the diabetics, insulin-mediated glucose metabolism was 12.14 ± 0,96 mg/kg . min (P < 0.01). In diabetics studied at euglycemic levels (group II) insulin-mediated glucose metabolism, 3.39 ± 0.30 mg/kg . min, was reduced even further. The metabolic clearance rate in the 19 diabetics, 3.31 ± 0.23 mg/kg . min, was reduced by 58% compared with controls, 7.83 ± 0.25 (P < 0.001). These results emphasize the severe degree of insulin resistance that exists in the insulin-dependent diabetics. Basal hepatic glucose production in the diabetic group, 2.96 ± 0.24 mg/kg . min, was 26% greater than in the controls, 2.35 ± 0.04 (P < 0.001). The fasting plasma glucose concentration displayed a strong positive correlation (r = 0.857, P < 0.001) with basal hepatic glucose production and was weakly and inversely correlated (r = -0.413, P = 0.07) with the basal glucose clearance. Following hyperinsulinemia, however, suppression of hepatic glucose production was ~ 95% in both diabetics and controls, suggesting that peripheral tissues are primarily responsible for the observed impairment in insulin-mediated glucose uptake. The present results indicate that impaired insulin action is a common feature of insulin-dependent diabetics, despite daily insulin requirements (35 ± 2 U/day) that would not clinically characterize them as being insulin resistant.

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