A desktop guide for the management of non-insulin-dependent diabetes mellitus (NIDDM): an update. European NIDDM Policy Group.
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Blood Glucose Self-Monitoring↗
Biomedical subjects
H M Krans
Publications and source records attributed to H M Krans.
Activation of the Ras/mitogen-activated protein kinase signaling pathway alone is not sufficient to induce glucose uptake in 3T3-L1 adipocytes.
The signal transduction pathway by which insulin stimulates glucose transport is largely unknown, but a role for tyrosine and serine/threonine kinases has been proposed. Since mitogen-activated protein (MAP) kinase is activated by insulin through phosphorylation on both tyrosine and threonine residues, we investigated whether MAP kinase and its upstream regulator, p21ras, are involved in insulin-mediated glucose transport. We did this by examining the time- and dose-dependent stimulation of glucose uptake in relation to the activation of Ras-GTP formation and MAP kinase by thrombin, epidermal growth factor (EGF), and insulin in 3T3-L1 adipocytes. Ras-GTP formation was stimulated transiently by all three agonists, with a peak at 5 to 10 min. Thrombin induced a second peak at approximately 30 min. The activation of p21ras was paralleled by both the phosphorylation and the activation of MAP kinase: transient for insulin and EGF and biphasic for thrombin. However, despite the strong activation of Ras-GTP formation and MAP kinase by EGF and thrombin, glucose uptake was not stimulated by these agonists, in contrast to the eightfold stimulation of 2-deoxy-D-[14C]glucose uptake by insulin. In addition, insulin-mediated glucose transport was not potentiated by thrombin or EGF. Although these results cannot exclude the possibility that p21ras and/or MAP kinase is needed in conjunction with other signaling molecules that are activated by insulin and not by thrombin or EGF, they show that the Ras/MAP kinase signaling pathway alone is not sufficient to induce insulin-mediated glucose transport.
1-Methyl-3-isobutylxanthine↗
Counterregulatory hormone responses during graded hyperinsulinemic euglycemia in conscious rats.
It has been suggested that hyperinsulinemia per se may affect the levels of some counterregulatory hormones in the absence of hypoglycemia. We studied the effect of graded hyperinsulinemia and concomitant increased glucose metabolism on the levels of counterregulatory hormones by means of the 5-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]-glucose infusion, in conscious rats. Insulin infusion rates (IIR) of 0, 0.5, 1, 3, and 16 mU/min, resulted in steady-state plasma insulin levels (mean +/- SEM) of 24 +/- 4, 44 +/- 3, 98 +/- 8, 418 +/- 48, and 6626 +/- 361 microU/ml, peripheral glucose uptake (PGU) of 3.1 +/- 0.2, 3.6 +/- 0.3, 5.4 +/- 0.3, 9.2 +/- 0.4, and 12.4 +/- 0.2 mg/min and hepatic glucose production (HGP) of 3.1 +/- 0.2, 2.4 +/- 0.4, 0.8 +/- 0.3, -0.1 +/- 0.2, and -0.5 +/- 0.3 mg/min, respectively. Plasma glucagon levels were half maximally suppressed between IIRs of 0.5 and 1 mU/min and maximally suppressed at 3 mU/min. The suppression exactly paralleled the inhibition of HGP (r = 0.87 +/- 0.04, p < 0.02) but not the stimulation of PGU (r = -0.66 +/- 0.12, p = NS). This suggests that the inhibition of HGP by insulin is at least partially mediated by a simultaneous suppression of plasma glucagon levels. The adrenal hormones corticosterone and epinephrine were not influenced during the clamp.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Recent clinical experience with aldose reductase inhibitors.
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Aldehyde Reductase↗
In vivo insulin responsiveness for glucose uptake and production at eu- and hyperglycemic levels in normal and diabetic rats.
UNLABELLED: Whole body glucose uptake (BGU) and hepatic glucose production (HGP) at maximal plasma insulin concentrations (+/- 5000 microU/ml) were determined by eu- (EC) (6 mM) and hyperglycemic (HC) (20 mM) clamps (120 min), combined with [3-3H]glucose infusion, in normal and streptozotocin-treated (65 mg/kg) 3-day diabetic, conscious rats. In normal rats, during EC, BGU was 12.4 +/- 0.4 mg/min and during HC, when urinary glucose loss was 0.54 +/- 0.09 mg/min, BGU was 25.5 +/- 1.6 mg/min. However, throughout the final 60 min of HC, glucose infusion rate (GIR) was not constant but a linear decline in time (r = -0.99) of 17%, P less than 0.0001, was observed indicating a hyperglycemia-induced desensitization process. In diabetic rats, during EC, BGU was 7.7 +/- 0.3 mg/min and during HC, BGU was 15.5 +/- 1.4 mg/min. Throughout the final 60 min of HC, GIR was constant, suggesting that the hyperglycemia-induced desensitization process was already completed. In normal and diabetic rats, HGP was similar: during EC 0.2 +/- 0.5 mg/min and 0.1 +/- 0.5 mg/min, and during HC 0.4 +/- 0.4 mg/min and 0.5 +/- 0.6 mg/min, respectively. In vitro adipocyte and muscle insulin receptor studies showed normal to increased receptor number and increased receptor autophosphorylation in diabetic compared to normal rats. IN CONCLUSION: (i) 3-day diabetic rats show, at maximal plasma insulin concentrations, insulin resistance to BGU, but not to HGP. The resistance to BGU is equally present (reduction of 38%) at eu- and hyperglycemic levels as compared to normal rats. (ii) 3-day diabetic rats reveal no defect in adipocyte and muscle insulin receptor function. These data indicate that the diabetes induced insulin resistance for BGU is at the post-receptor level and due to a decreased maximal capacity (Vmax) for glucose uptake, with no change in affinity, or Km.
Adipose Tissue↗
An Arg for Gly substitution at position 31 in the insulin receptor, linked to insulin resistance, inhibits receptor processing and transport.
In a patient with Leprechaunism, we have characterized a new mutation in the insulin receptor substituting Arg for Gly at position 31. The proband, the mother, and the maternal grandfather were heterozygous for the mutation. Fibroblasts of the proband show a strongly reduced number of high affinity insulin receptors on the cell surface, whereas fibroblasts of the healthy mother and grandfather show moderately reduced insulin receptor numbers. In the other family members neither the binding defect nor the Arg31 mutation was found. The Arg31-mutant receptor was overexpressed in Chinese hamster ovary cells. In these cells the mutant alpha beta-proreceptor was not proteolytically cleaved and no transport to the cell surface took place. The proreceptor was unable to bind insulin and to undergo autophosphorylation. In addition, the proreceptor was not recognized by monoclonal antibodies directed against conformation-dependent epitopes. These findings suggest that the Gly31 to Arg31 mutant is involved in the insulin receptor dysfunction seen in the Leprechaun patient. The mutation seems to alter the conformation of the receptor in such way that the transport of the proreceptor to the Golgi compartment, where proteolytical processing occurs, is inhibited.
Alleles↗
Fluoxetine increases insulin action in obese nondiabetic and in obese non-insulin-dependent diabetic individuals.
Insulin resistance contributes to the metabolic defects in non-insulin-dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. The serotonin-reuptake inhibiting agent fluoxetine has recently been recognized as an anorectic agent. The effect of fluoxetine on insulin action has not yet been determined. In a double blind placebo controlled crossover study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinemic euglycemic clamp technique with infusion of 3-3H-glucose in eight obese NIDDM and in eight obese nondiabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu 180.5 +/- 25.8 vs 225.3 +/- 39.9 mU/l, P less than 0.05), but not in nondiabetics (140 +/- 15.3 vs 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Basal hepatic glucose production (HGP) was reduced after fluoxetine in both NIDDM (9.45 vs 10.37 mumol/kg/min) and in nondiabetics (8.57 vs 9.16 mumol/kg/min), although the difference was only significant in nondiabetics (P less than 0.05). Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and nondiabetics. When nondiabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P less than 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production is completely suppressed (HGP0) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
C-Peptide↗
Fluoxetine increases insulin action in obese type II (non-insulin dependent) diabetic patients.
Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinaemic-euglycaemic clamp technique with infusion of 3-[3H]-glucose in eight obese NIDDM patients and in eight obese non-diabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu: 180.5 +/- 25.8 vs. 225.3 +/- 39.9 mU/l, P < 0.05), but not in non-diabetics (140 +/- 15.3 vs. 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and non-diabetics. When non-diabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P < 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production (HGP) is completely suppressed (HGP0) (P < 0.01). In conclusion, fluoxetine improves peripheral and hepatic insulin action in obese insulin-resistant subjects irrespective of its weight lowering effect.
Blood Glucose↗
Biological action of pancreatic amylin: relationship with glucose metabolism, diabetes, obesity and calcium metabolism.
Amylin, also called islet amyloid polypeptide (IAPP), or diabetes-associated peptide (DAP) is a recently discovered 37 amino acid polypeptide which has been shown to be co-secreted with insulin from the pancreatic beta-cell. The peptide turned out to be the major constituent of pancreatic amyloid deposits which are frequently found in the pancreas of type II diabetic patients. Therefore, a role for amylin in the aetiology of type II diabetes was hypothesized. To investigate this possibility, several studies have been performed to elucidate whether amylin is able to impair insulin secretion and action, two characteristic features of type II diabetes mellitus. These studies suggest that it is unlikely that amylin has a direct inhibitory effect on insulin secretion. Amyloid deposits, however, which are derived from the in situ polymerization and precipitation of amylin, may impair beta-cell function during type II diabetes by damaging and covering beta-cells. Furthermore, it has been shown that amylin has the potential to antagonize the action of insulin on glucose metabolism by increasing hepatic glucose production and by decreasing muscle, but not adipocyte glucose uptake. For these reasons, it has been suggested that amylin might be involved in the pathophysiology of type II diabetes and obesity, disease states which are characterized by abnormal beta-cell function and insulin resistance. In addition, amylin was shown to induce hypocalcaemia by inhibiting osteoclast-mediated bone resorption in a calcitonin-like manner. Therefore, amylin is likely to be involved in both the modulation of glucose and calcium metabolism.
Amyloid↗
A leucine to proline mutation at position 233 in the insulin receptor inhibits cleavage of the proreceptor and transport to the cell surface.
We have previously shown that a homozygous mutation encoding a substitution of proline for leucine at position 233 in the insulin receptor is linked with the syndrome of leprechaunism, being a lethal form of insulin resistance in newborn children. Specific binding of insulin and insulin-stimulated autophosphorylation of the insulin receptor are nearly absent in fibroblasts from the leprechaun patient. To examine the molecular basis of the observed insulin receptor abnormalities, CHO cell lines overexpressing mutant insulin receptors were made by transfection. The results show that the mutation inhibits cleavage and transport of the proreceptor from intracellular sites to the cell surface. As the mutant receptor is poorly precipitated by two different monoclonal antibodies recognizing epitopes on undenatured wild-type alpha-subunits, the mutation probably affects overall folding of the alpha-subunit. The mutant proreceptor is unable to bind insulin and exhibits no insulin-stimulated autophosphorylation. These data explain the abnormalities seen in the patient's fibroblasts. Pulse-chase labeling experiments on transfected cells show that the mutant precursor has an extended half-life (approximately 5 h) compared to the precursor of wild-type insulin receptors (approximately 2 h). This mutation is the first example of a naturally occurring mutation in the insulin receptor which completely blocks cleavage of the proreceptor and transport to the cell surface.
Animals↗
[Molecular heterogeneity of congenital forms of insulin resistance].
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Endocrine System Diseases↗
Amylin-induced in vivo insulin resistance in conscious rats: the liver is more sensitive to amylin than peripheral tissues.
UNLABELLED: Amylin is a polypeptide of 37 amino acids, predominantly synthesized in pancreatic Beta cells. The peptide was suggested to be dysregulated in Type 2 (non-insulin-dependent) diabetes mellitus and it antagonized certain actions of insulin in vitro in rat muscle. This led to speculation that amylin is involved in the pathogenesis of Type 2 diabetes. We have examined the in vivo effects of rat amylin, amidated at the carboxy-terminus, on insulin-mediated carbohydrate metabolism in conscious rats, using the hyperinsulinaemic (+/- 1 nmol/l) euglycaemic (6 mmol/l) clamp technique combined with [3-3H]-glucose infusion. Basal plasma amylin levels were less than or equal to 75 pmol/l. Applied amylin levels of 220 +/- 75 pmol/l (infusion rate of 12.5 pmol/min) antagonized only the insulin action on liver, resulting in a 100% increase of hepatic glucose output. Amylin levels of 4750 +/- 750 pmol/l (infusion rate of 125 pmol/min) induced a 250% increase of insulin-inhibited hepatic glucose output and, in addition, a 30% decrease of insulin-stimulated peripheral glucose up-take. Amylin did not affect: 1) the metabolic clearance rate of insulin, 2) the levels of plasma glucagon, epinephrine, norepinephrine, and corticosterone, 3) in vitro insulin binding and insulin-stimulated receptor autophosphorylation. This suggests that amylin antagonizes insulin action via binding to a yet unknown receptor. IN CONCLUSION: amylin causes in vivo insulin resistance and the liver seems the predominant organ regulated by this hormone. The in vivo effects of amylin mimic the pathophysiological abnormalities of insulin action in Type 2 diabetes.
Amyloid↗
Glucose disposal and intermediary metabolism during one year of continuous subcutaneous insulin infusion (CSII).
To study the effects of CSII on insulin action and intermediary metabolism, seven type 1 diabetic patients (duration 17 +/- 4 (SEM) years), underwent sequential euglycemic clamps 1/4, 6 and 12 months after changing from conventional insulin treatment to continuous subcutaneous insulin infusion (CSII); seven healthy subjects served as controls. For at least 14 h before the study, blood glucose was maintained between 4-10 mmol/l in the patients by intravenous insulin infusion, to avoid negatively biased clamp measures. A metabolite profile was taken in the basal state and during euglycemic hyperinsulinemia. At 1/4 month insulin sensitivity was decreased in the patients (ED50 82 +/- 14 vs 52 +/- 4 mU/l in controls, P less than 0.02), whereas insulin responsiveness was normal. During the course of one year, no change towards control values was found for insulin-stimulated glucose disposal. Concomitantly, HbA1 did not change either, and remained elevated (1/4 month 11.1 +/- 0.7%, 12 months 10.0 +/- 0.9% vs 6.5 +/- 0.3% in controls, P less than 0.01). Regarding basal intermediary metabolism, triglycerides became significantly improved (1/4 month 1.32 +/- 0.13 mmol/l, 12 months 0.70 +/- 0.05 mmol/l, P less than 0.05, vs 0.70 +/- 0.08 mmol/l in controls). The acetoacetate/3-OH-butyric acid ratio increased from 0.10 at 3 to 0.26 at 12 months, which was similar to controls. The absolute levels of acetoacetate and 3-OH-butyric acid remained elevated 2-3 fold. For other basal metabolite levels no systematic trend for improvement was found for 1/4 to 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Whole body and hepatic insulin action in normal, starved, and diabetic rats.
In normal (N), 3-days starved (S), and streptozotocin-treated (65 mg/kg) 3-days diabetic (D) rats we examined the in vivo dose-response relationship between plasma insulin levels vs. whole body glucose uptake (BGU) and inhibition of hepatic glucose production (HGP) in conscious rats, as determined with the four-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]glucose infusion. Twelve-hour fasting (basal) HGP was 3.0 +/- 0.2, 2.1 +/- 0.2, and 5.4 +/- 0.5 mg/min in N, S, and D rats, respectively. Next, all rats were clamped at matched glycemia (6 mM). Lowering plasma glucose in D rats from +/- 20 to 6.0 mM did not increase plasma norepinephrine, epinephrine, glucagon, and corticosterone levels. For BGU, insulin sensitivity was increased (70 +/- 11 microU/ml) in S and unchanged (113 +/- 21 microU/ml) in D compared with N rats (105 +/- 10 microU/ml). Insulin responsiveness was unchanged (12.4 +/- 0.8 mg/min) in S and decreased (8.5 +/- 0.8 mg/min) in D compared with N rats (12.3 +/- 0.7 mg/min). For HGP, insulin sensitivity was unchanged (68 +/- 10 microU/ml) in S and decreased (157 +/- 21 microU/ml) in D compared with N rats (71 +/- 5 microU/ml). Insulin responsiveness was identical among N, S, and D rats (complete suppression of HGP). In summary, 1) insulin resistance in D rats is caused by hepatic insensitivity and by a reduction in BGU responsiveness. 2) S rats show normal hepatic insulin action, but insulin sensitivity for BGU is increased. Therefore, S and D rats both suffering from a comparable catabolic state (10-15% body wt loss in 3 days) show opposite effects on in vivo insulin action. This indicates that in vivo insulin resistance in D rats is not caused by the catabolic state per se.
Animals↗
In vivo relationship between insulin clearance and action in healthy subjects and IDDM patients.
The relationship between plasma clearance rate of insulin (PCR) and insulin-stimulated glucose disposal was investigated in 15 healthy subjects and 30 insulin-dependent diabetes mellitus (IDDM) patients with the sequential euglycemic (5 mM) clamp technique (insulin infusion rates of 0.5, 1, 2, and 5 mU.kg-1.min-1 in 2-h steps). In IDDM patients, insulin-stimulated glucose disposal was decreased at low insulinemia (steps 1-3), whereas at maximal insulinemia (step 4), insulin action was normal. In the healthy subjects, strong positive correlations were found for PCR versus steady-state glucose infusion rate (SSGIR): r = 0.71 (P less than 0.005), 0.72 (P less than 0.005), 0.72 (P less than 0.005), and 0.78 (P less than 0.001) for steps 1-4, respectively. In contrast, in the IDDM patients, no relationship was observed: r = 0.01, -0.03, 0.06, and 0.01 (NS) for steps 1-4, respectively. In univariate analyses of PCR, no differences were found between patient subgroups with values for percentage of tracer binding below or above 5% or insulin-antibody-binding capacities and equilibrium constants below or above the median. In multiple regression models, adjusting for insulin antibodies, preceding glycemic control (HbA1 or fructosamine), and duration of IDDM, correlations for PCR versus SSGIR remained nonsignificant. In conclusion, insulin action is correlated to insulin clearance in healthy subjects, suggesting a functional relationship from an in vivo perspective. No such relationship was present in patients with IDDM, even after adjusting for insulin antibodies, preceding glycemic control, and duration of IDDM.
Adult↗
Insulin resistance in type 1 (insulin-dependent) diabetes: dissimilarities for glucose and intermediary metabolites.
To study insulin action on intermediary metabolism in relation to glucose disposal in Type 1 (insulin-dependent) diabetes, 29 patients and 15 control subjects underwent sequential euglycemic clamps (insulin infusion rates 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in 2 hour periods). Dose-response curves were constructed for insulin-stimulated glucose disposal. Metabolite profiles were determined in the basal state, and during submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulinaemia. For at least 11 hours preceding the study, blood glucose levels were maintained between 4 and 10 mmol/l in the patients. In the basal state, when at matched glycemia hepatic glucose production is known to be similar in patients and control subjects, glucose, glycerol, free fatty acids and glucagon were comparable, whereas differences were found for alanine (-29%, diabetic vs. control subjects), lactate (-24%), acetoacetate (+270%), 3-hydroxybutyrate (+260%) and insulin (+210%; all p less than 0.02). At submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulin levels, metabolite levels were comparable, except alanine (-20% diabetic vs. control subjects, p less than 0.001). Glucose disposal rates, however, were decreased in patients at submaximal insulin levels (ED50 73 +/- 10 vs. 54 +/- 4 mU/l in control subjects, p less than 0.01 whereas maximal glucose disposal was similar (61 +/- 3 vs. 65 +/- 3 mumol.kg-1.min-1). In conclusion, in Type 1 diabetes: (a) changes in basal levels of intermediary metabolites were present, despite 11 hours of antecedent euglycemia; (b) in contrast to glucose disposal at submaximal insulinaemia, no major difference existed in insulin's efficacy on intermediary metabolism.
Adult↗
A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance.
We have determined the primary structure of a mutant insulin receptor of a leprechaun patient born from a consanguineous marriage. A characteristic feature of leprechaunism is an extreme resistance to insulin. In this patient the insulin resistance seems to result from an observed lack of insulin binding to intact cells. Solubilization of cells in non-ionic detergents leads to the appearance of insulin receptors which can bind insulin. However, the insulin-stimulated autophosphorylation of the receptor's beta subunit is markedly reduced. Cloning and sequencing of cDNA derived from insulin receptor mRNA of this patient revealed a leucine-to-proline mutation at position 233 in the alpha subunit. By means of DNA amplification we found that the patient is homozygous for this mutation and that the parents and two grandparents from the consanguineous line are heterozygous. The heterozygous individuals all show decreased insulin binding to cultured fibroblasts. In addition, they are mildly insulin resistant in vivo. These observations show a linkage between the leucine-to-proline mutation and the observed insulin resistance in this family. We therefore conclude that the mutation in the homozygous form is responsible for the extreme insulin resistance in the leprechaun patient. The mutation for the first time characterizes a region in the insulin receptor which seems to be involved in transmitting the insulin binding signal to the tyrosine kinase domain.
Cells, Cultured↗
The course and determinants of insulin action in type 1 (insulin-dependent) diabetes mellitus.
The course and determinants of insulin action were investigated in 8 newly diagnosed Type 1 (insulin-dependent) diabetic patients, who were studied every 3 months for one year, and in three groups of 8 patients each with 5, 10 and 20 years diabetes, studied once. Fifteen healthy subjects matched for age, sex and body weight served as control subjects. Dose-response curves were constructed using sequential euglycaemic (5.0 mmol/l) clamps (insulin infusion rates: 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in periods of 2h). After 1/2 month of insulin treatment, insulin responsiveness was normal, but sensitivity was decreased (ED50 70 +/- 7 mU/l (SEM) vs 54 +/- 4 mU/l in control subjects, p less than 0.05). After 6 months, insulin sensitivity was improved (ED50 57 +/- 4 mU/l, p less than 0.01 vs 1/2 month and not significant (NS) vs control subjects); but after 9 and 12 months, it was reduced again, similarly to 0.5 month. Insulin responsiveness remained normal at all time-points. In the three groups of patients with longstanding diabetes, impaired insulin sensitivity with normal responsiveness was noted also (ED50 73 +/- 9 mU/l, p less than 0.02 vs control subjects). At 6, 9 and 12 months, glycaemic control (HbA1) and insulin dose were inverse correlates for insulin action; in patients with longstanding disease, this was noted for HbA1 and body weight, in control subjects for body weight. In conclusion, decreased insulin sensitivity re-develops in Type 1 diabetes within the first year following an initial improvement.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗