Insulin Resistance and Insulin-Dependent Diabetes Mellitus

Pedersen, Oluf; Beck‐Nielsen, Henning

doi:10.2337/diacare.10.4.516

Cited by 34 publications

(13 citation statements)

References 64 publications

(93 reference statements)

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“…Furthermore, changes in serum insulin within the physiological range with a 2.8-fold increase over a 24-h period did not contribute to the acute regulation of total GS activity and GS mRNA and immunoreactive protein abundance in muscle but normalized the muscle GS activation in diabetic patients. Hence, the present data suggest that the impaired glycogen synthesis of skeletal muscle from Type 1 diabetic patients in poor metabolic control [1][2][3] is caused by post-translational modifications of the GS enzyme which may be secondary to metabolic derangements [3,7]. This interpretation of results is compatible with the study of Vuorinen-Markkola et al [28] demonstrating that 24 h of hyperglycaemia induces a severe impairment of whole-body non-oxidative glucose metabolism in Type I diabetic patients.…”

Section: Discussionsupporting

confidence: 90%

“…[Diabetologia (1994) 37: 82-90] completely reversed during remission of the disease in recent-onset Type i diabetes [4] or nearly ameliorated by improved glycaemic control in patients with longterm diabetes [5,6]. It has, therefore, been suggested that the insulin resistance in Type 1 diabetes, at least in part, is secondary to metabolic derangements [3,7]. Previous studies of the cellular insulin resistance of peripheral tissues from patients with Type i diabetes have shown decreased insulin binding to musclederived insulin receptors but normal receptor kinase activity [8] and decreased glucose transport and oxida-tion in adipose tissue [9].…”

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confidence: 99%

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Expression of glycogen synthase and phosphofructokinase in muscle from Type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

et al. 1994

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SummaryThe aim of the present study was to determine whether short-term appropriate insulinization of Type i (insulin-dependent) diabetic patients in longterm poor glycaemic control (HbAlc > 9.5 %) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 + 0.8 to 8.7+0.8mmol/1 whereas fasting serum insulin increased from 59 + 8 to 173 + 3 pmol/1). Before intensified insulin therapy, analysis of muscle biopsies from diabetic patients showed a normal total glycogen synthase activity but a 48 % decrease (p --0.006) in glycogen synthase fractional velocity (0.1 mmol/1 glucose 6-phosphate) (FV01) and a 45 % increase (p = 0.01) in the half-maximal activation constant of glycogen synthase (A0.5). The activity of phosphofructokinase and the specific mRNA and immunoreactive protein levels of both glycogen synthase and phosphofructokinase were similar in the two groups. The 2.8-fold increase in serum insulin levels and the halving of the plasma glucose level for at least 15 h were associated with a normalization of glycogen synthase fractional activity (FV0.I) and of the half-maximal activation constant (A05) whereas the enzyme activity of phosphofructokinase and the mRNA and protein levels of both glycogen synthase and phosphofructokinase remained normal. In conclusion: 1) Reduced allosterical activation of glycogen synthase in muscle of Type 1 diabetic patients in poor metabolic control occurs in the presence of normal total activity as well as normal immunoreactive protein mass and mRNA level of glycogen synthase. 2) Changes in serum insulin within the physiological range play no role in the short-term regulation of glycogen synthase mRNA and protein abundance in muscle from Type I diabetic patients. [Diabetologia (1994) 37: 82-90]

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Expression of glycogen synthase and phosphofructokinase in muscle from Type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

et al. 1994

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“…Under insulin treatment, however, type 1 diabetes mellitus patients may also have insulin resistance, especially when obesity is also present (10).…”

Section: T He Association Of Hyperandrogenism and Clini-mentioning

confidence: 99%

High Prevalence of the Polycystic Ovary Syndrome and Hirsutism in Women with Type 1 Diabetes Mellitus1

Escobar‐Morreale¹,

Roldán

Barrio

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown.Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles.Thirty-three patients (38.8%) presented hyperandrogenic disorders (16 had PCOS, and 17 had hirsutism without menstrual dysfunction). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum androstenedione levels, but had normal serum sex hormone-binding globulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 diabetic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hyperandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control.In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hirsutism. (J Clin Endocrinol Metab 85: 4182-4187, 2000)

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“…Even if the primary metabolic defect of type 1 diabetes (T1DM) is considered to be insulin deficiency, a number of studies have suggested that a certain degree of insulin resistance is also present in patients with T1DM (9,10,11,26,31,47). An increased intramyocellular triglyceride (IMCL) content has been hypothesized to be the pathogenic event responsible for the development of insulin resistance in T2DM and in the insulin resistance syndrome (28).…”

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confidence: 99%

Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes

Perseghin

Lattuada

Danna

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

159

131

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Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2 H2]glucose and 1 H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 Ϯ 0.6 and 3.2 Ϯ 0.8 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ) similar to OFF (5.3 Ϯ 0.4 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ) compared with NOR (8.5 Ϯ 0.5 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.001). Soleus IMCL content was increased in T1DM (112 Ϯ 15 AU), T2DM (108 Ϯ 10 AU) and OFF (82 Ϯ 13 AU) compared with NOR (52 Ϯ 7 AU, P Ͻ 0.05) and the result was inversely proportional to the MCR (R 2 ϭ 0.27, P Ͻ 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R 2 ϭ 0.57, P Ͻ 0.001). Fasting plasma adiponectin was reduced in T2DM (7 Ϯ 1 g/ml, P ϭ 0.01) and OFF (11 Ϯ 1 g/ml, P ϭ 0.03) but not in T1DM (25 Ϯ 6 g/ml), whose plasma level was increased with respect to both OFF (P ϭ 0.03) and NOR (16 Ϯ 2 g/ml, P ϭ 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear. intramyocellular triglyceride content; leptin; magnetic resonance spectroscopy

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Insulin Resistance and Insulin-Dependent Diabetes Mellitus

Cited by 34 publications

References 64 publications

Expression of glycogen synthase and phosphofructokinase in muscle from Type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

Expression of glycogen synthase and phosphofructokinase in muscle from Type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

High Prevalence of the Polycystic Ovary Syndrome and Hirsutism in Women with Type 1 Diabetes Mellitus1

Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes

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