Hepatic and peripheral insulin resistance: A common feature of Type 2 (non-insulin-dependent) and Type 1 (insulin-dependent) diabetes mellitus

Abstract

Hepatic glucose production (3H-glucose technique) and insulin-mediated glucose uptake (insulin clamp technique) were measured in 38 Type 2 (non-insulin-dependent) and 11 Type 1 (insulin-dependent) diabetic patients. Fasting plasma glucose concentration was 8.3 +/- 0.5 mmol/l in the former, and 9.6 +/- 1.3 mmol/l in the latter group; the respective fasting plasma insulin levels were 19 +/- 2 mU/l (p less than 0.005 versus 13 +/- 1 mU/l in 33 age-matched control subjects), and 9 +/- mU/l (p less than 0.01 versus 14 +/- 1 mU/l in 36 younger control subjects). In the fasting state, hepatic glucose production was slightly increased (15%, 0.1 greater than p greater than 0.05) in the Type 2 diabetic patients and markedly elevated (65%, p less than 0.001) in the Type 1 patients compared with their respective control groups. In both groups of diabetic subjects, the rates of hepatic glucose production were inappropriately high for the prevailing plasma glucose and insulin levels, indicating the presence of hepatic resistance to insulin. Basal plasma glucose clearance was also significantly reduced in both the Type 2 (34%) and the Type 1 (14%) diabetic subjects. The fasting plasma glucose concentration correlated directly with hepatic glucose production, and inversely with plasma glucose clearance. During the insulin clamp, plasma insulin was maintained at approximately 100 mU/l in all groups, while plasma glucose was maintained constant at the respective fasting levels. Total glucose uptake was reduced in both the Type 2 (4.57 +/- 0.31 versus 6.39 +/- 0.25 mg . min -1 . kg -1 in the control subjects, p less than 0.01) and the Type 1 (4.77 +/- 0.48 versus 7.03 +/- 0.22 mg . min -1 . kg -1, p less than 0.01)diabetic patients. Insulin-stimulated glucose clearance was reduced to a similar extent in Type 2 (54%) and Type 1 (61%) diabetic subjects, and correlated directly with fasting glucose clearance. These results show that insulin resistance is a common feature of both types of diabetes and can be demonstrated in the basal as well as the insulin-stimulated state. Both hepatic and peripheral resistance to the action of insulin contribute to diabetic hyperglycaemia.

Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes

“…In these patients the reduced IHF content is associated with markers of enhanced whole-body fat oxidation, possibly due to the local effects of the higher glucagon/hepatic insulin ratio on liver substrate disposal. Insulin resistance characterises type 2 diabetes but several studies have shown that a certain degree of insulin resistance is also present in patients with type 1 diabetes [18], especially when metabolic control is poor [19]. In agreement with the hypothesis that ectopic fat accumulation may be related to impaired insulin action, an increased IMCL content in association with peripheral insulin resistance was reported in patients with type 1 diabetes as well as in patients with type 2 diabetes and their relatives [4].…”

The biochemical basis of increased hepatic glucose production in a mouse model of type 2 (non-insulin-dependent) diabetes mellitus

“…cose production (HGP) [1][2][3][4][5]. Although in the past HGP has been overestimated due to failure to adequately prime the glucose pool [6], there is no doubt that a hepatic defect is present, since even a normal HGP is abnormal in the presence of elevated glucose and insulin.…”

Characterization of an Early Decline in Baseline Plasma Glucose Concentration after Acute Insulin Elevation during Euglycemic Hyperinsulinemic Clamp in Patients with Type 2 Diabetes Mellitus.

“…This assumption was further supported by the present findings that both were significantly correlated with one another. HOMA index consists of (FPG) x (FIRI), in which fasting plasma glucose is well known to correlate with hepatic glucose output [3,5,22], and fasting plasma insulin levels potentially relate to the hepatic clearance of insulin. From these considerations, we believe that HOMA index represents hepatic insulin resistance rather than a skeletal muscle insulin resistance.…”

“…IT is well established that patients with type 2 diabetes mellitus are resistant to insulin-mediated glucose utilization [1][2][3][4][5][6]. While skeletal muscle is believed to be the major site responsible for insulin resistance [4], the contribution of the liver to wholebody insulin resistance is poorly understood.…”

“…To date, however, hepatic insulin resistance in type 2 diabetes remains controversial; some investigators have found that the insulininduced suppression of hepatic glucose output is impaired [5][6][7][8][9], whereas others have not confirmed these findings [3,10]. In the euglycemic hyperinsulinemic clamp method, skeletal muscle glucose uptake can be assumed to approximate the exogenously infused glucose under a plasma concentration of insulin that allows the complete suppression of hepatic glucose output.…”