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  • 1
    ISSN: 0888-7543
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 31 (1988), S. 186-187 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Type2 (non-insulin-dependent) diabetes mellitus sulfonylurea ; metformin ; insulin ; secondary drug failure ; energy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Which therapy should be used in Type 2 (noninsulin-dependent) diabetic patients with “secondary sulfonylurea failure”, insulin or a combination of sulfonylurea and metformin? To address this question, we have compared the effect of 6 months of insulin therapy twice daily with that of a combination of glibenclamide and metformin in 24 Type 2 diabetic subjects, who no longer responded to treatment with sulfonylureas. Both treatments resulted in an equivalent 30% improvement in mean daily blood glucose (p〈0.001), without significant effect on serum lipids. Insulin improved glycaemic control primarily by reducing basal hepatic glucose production (p〈0.05), but had no significant effect on peripheral glucose metabolism. The combination of glibenclamide and metformin enhanced significantly total body glucose metabolism (p〈0.05), predominantly by stimulating the non-oxidative pathway. Neither insulin nor the combination therapy altered B-cell response to a test meal. Insulin therapy resulted in a 6% increase in body weight, 63% of which was accounted for by increased fat mass. Although body weight was unchanged during sulfonylurea/metformin therapy, lean body mass and energy expenditure decreased significantly (p〈0.05). We conclude that insulin and glibenclamide/metformin have different long-term effects on glucose and energy metabolism in Type 2 diabetes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; insulin sensitivity ; peripheral glucose utilisation ; non-esterified fatty acids ; risk group
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mechanisms underlying insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus are not fully understood. An enhanced lipid/non-esterified fatty acid oxidation could provide an explanation. To test this hypothesis we examined the relationship between glucose and lipid metabolism in 44 first-degree relatives (28 glucose-tolerant and 16 glucose-intolerant) of Type 2 diabetic patients and in 18 healthy control subjects. Total body glucose disposal was impaired among both glucose-tolerant and glucose-intolerant relatives compared with control subjects (36.3±3.8 and 30.4±2.7 vs 47.7±3.4 μmol · kgLBM/s-1· min−1; p 〈 0.05). The impairment in glucose disposal among the relatives was primarily accounted for by impaired non-oxidative glucose metabolism (14.8±3.0 and 12.5±1.8 vs 25.3±3.1 μmol · kgLBM−1 · min−1; p 〈0.05). Plasma non-esterified fatty acid concentrations were similar in both glucose-tolerant and glucose-intolerant relatives and control subjects (646±36,649±43 and 615±41 μmol/l) and showed the same degree of suppression by insulin (99±8, 86±7 and 84±9 μmol/l). Basal lipid oxidation was similar in all groups (1.29±0.09, 1.52±0.13 and 1.49±0.21 μmol · kgLBM−1· min−1). Furthermore, insulin suppressed lipid oxidation to the same degree in glucose-tolerant, glucose-intolerant relatives and control subjects (0.65±0.13, 0.88±0.15 and 0.59±0.09μmol · kgLBM−1 · min−1). An inverse correlation between plasma non-esterified fatty acid concentration and total body glucose disposal was observed in the group of control subjects (r=−0.540; p〈0.05), but not among the relatives (r=0.002; p=N.S.). In conclusion the present data challenge the view that the “glucose-fatty acid cycle” contributes to the insulin resistance seen in first-degree relatives of patients with Type 2 diabetes.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; insulin resistance ; first-degree relatives ; islet amyloid polypeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study whether abnormal secretion of islet amyloid polypeptide is involved in the development of insulin resistance and impaired insulin secretion in Type 2 (noninsulin-dependent) diabetes mellitus, we measured islet amyloid polypeptide concentrations in 56 first-degree relatives of Type 2 diabetic subjects and in 10 healthy control subjects. Fasting islet amyloid polypeptide concentrations were similar in control subjects, glucose-tolerant and glucose-intolerant relatives (8±1, 9±1 and 11±2 fmol/ml; p=NS). The area under the islet amyloid polypeptide curve measured during an oral glucose load was larger in glucose-intolerant relatives (115±13 fmol/ml) compared to glucose tolerant relatives and control subjects (88±3 and 79±12 fmol/ml; p〈0.05). The insulin response during the oral glucose load was inversely correlated with the rate of glucose disposal measured during a euglycaemic hyperinsulinaemic clamp (r=−0.725; p〈0.01), while no significant correlation was observed between the corresponding values for islet amyloid polypeptide and glucose disposal (r=−0.380; p=NS). Hypersecretion of islet amyloid polypeptide is observed in glucose-intolerant first-degree relatives of patients with Type 2 diabetes. Since these patients are characterized by insulin resistance and abnormal first-phase insulin secretion, the putative role of islet amyloid polypeptide in the development of these abnormalities remains to be established. It is however, unlikely that islet amyloid polypeptide is involved in the development of insulin resistance as insulin-resistant relatives with normal glucose-tolerance showed normal islet amyloid polypeptide concentrations.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Genetics ; DNA polymorphism ; glucose ; phosphorylation ; glycolysis ; chromosome 2 ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type 2 (non-insulin-dependent) diabetes mellitus is characterized by decreased levels of glucose 6-phosphate in skeletal muscle. It has been suggested that the lower concentrations of glucose 6-phosphate contribute to the defect in glucose metabolism noted in muscle tissue of subjects with Type 2 diabetes or subjects at increased risk of developing Type 2 diabetes. Lower levels of glucose 6-phosphate could be due to a defect in glucose uptake, or phosphorylation, or both. Hexokinase II is the isozyme of hexokinase that is expressed in skeletal muscle and is responsible for catalysing the phosphorylation of glucose in this tissue. The recent demonstration that mutations in another member of this family of glucose phosphorylating enzymes, glucokinase, can lead to the development of Type 2 diabetes prompted us to begin to examine the possible role of hexokinase II in the development of this genetically heterogeneous disorder. As a first step, we have cloned the human hexokinase II gene (HK2) and mapped it to human chromosome 2, band p13.1, by fluorescence in situ hybridization to metaphase chromosomes. In addition, we have identified and characterized a simple tandem repeat DNA polymorphism in HK2 and used this DNA polymorphism to localize this gene within the genetic linkage map of chromosome 2.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Key words Glucagon receptor gene ; non-insulin-dependent diabetes mellitus ; impaired glucose tolerance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A heterozygous polymorphism changing GGT40 (Gly) to AGT40 (Ser) (Gly40Ser) in the glucagon receptor gene was reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM). A possible involvement of this polymorphism in impaired glucose tolerance was also suggested in a French population. To replicate this finding we screened 311 unrelated NIDDM patients, 101 unrelated individuals with impaired glucose tolerance and 306 control subjects for the presence of the Gly40Ser polymorphism by use of polymerase chain reaction-restriction fragment length polymorphism in a Finnish population. None of the NIDDM or impaired glucose tolerant patients had this polymorphism. Instead, four of the control subjects (1.3 %) were heterozygous carriers of the polymorphism (NS). The age, body mass index, 2-h blood glucose level, 2-h insulin level, and incremental insulin area of the four subjects with this polymorphism were similar to those of the control subjects homozygous for the wild type. Taken together, the data do not support the suggested involvement of the Gly40Ser polymorphism in impaired glucose tolerance and the hypothesis of an association between NIDDM and the glucagon receptor gene in this population. [Diabetologia (1995) 38: 1246–1248]
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Microalbuminuria ; insulin resistance syndrome ; insulin sensitivity ; euglycaemic hyperinsulinaemic clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microalbuminuria has recently been associated with insulin resistance in both insulin-dependent and non-insulin-dependent (NIDDM) diabetes mellitus. To establish whether microalbuminuria in non-diabetic subjects as well is associated with insulin resistance and associated abnormalities in glucose and lipid metabolism, oral glucose tolerance tests were performed with measurement of urinary albumin excretion rate, lipids and lipoproteins in 582 male non-diabetic first-degree relatives of patients with NIDDM. In addition, insulin sensitivity was assessed in 20 of these subjects with the euglycaemic hyperinsulinaemic clamp technique. Abnormal albumin excretion rate (AER), defined as AER 15–200 Μg/min, was associated with higher systolic blood pressure (p〈0.05), higher fasting glucose values (p〈0.05), lower HDL-cholesterol (p〈0.05) and lower apolipoprotein A-I (p〈0.05) concentrations than observed in subjects with normal AER. The rate of glucose metabolism was lower in subjects with abnormal compared to subjects with normal albumin excretion rate (38.0±2.8 vs 47.3±2.4 Μmol·kg lean body mass−1. min−1; p=0.028). This difference was almost completely accounted for by a reduction in non-oxidative glucose metabolism (17.7±1.9 vs 27.4±2.7 Μmol·kg lean body mass−1. min−1; p = 0.010), which correlated inversely with the AER (r=−0.543; p=0.013). These results suggest that in non-diabetic individuals genetically predisposed to NIDDM, abnormal AER is associated with insulin resistance and abnormalities in glucose and lipid metabolism.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Key words Insulin resistance ; lipase activities ; lipoproteins.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities of hepatic and lipoprotein lipase and the levels of lipo- and apoproteins were compared in two groups of normoglycaemic men representing the highest (n = 18) and lowest (n = 15) fasting insulin quintiles of first degree male relatives of non-insulin-dependent diabetic patients. The high insulin group representing insulin-resistant individuals had significantly lower post-heparin plasma lipoprotein lipase activity than the low insulin group (14.2 ± 4.0 vs 20 ± 5.8 μmol NEFA · ml−1· h−1, p 〈 0.001); hepatic lipase activity did not differ between the two groups (24.2 ± 11 vs 18.0 ± 5.3 μmol NEFA · ml−1· h−1, NS). The lipoprotein lipase/hepatic lipase ratio in the high insulin group was decreased by 66 % as compared to the low insulin group (0.75 ± 0.57 vs 1.25 ± 0.65, p 〈 0.01). In the high insulin group both total and VLDL triglycerides were higher than in the low insulin group (1.61 ± 0.57 vs 0.86 ± 0.26 mmol/l, p 〈 0.001 and 1.00 ± 0.47 vs 0.36 ± 0.16 mmol/l, p 〈 0.001, respectively) whereas HDL cholesterol and HDL2 cholesterol were lower (1.20 ± 0.30 vs 1.43 ± 0.22 mmol/l, p 〈 0.05 and 0.49 ± 0.21 vs 0.71 ± 0.17 mmol/l, p 〈 0.05, respectively). Total cholesterol, LDL cholesterol or HDL3 cholesterol did not differ between the two groups. The mean particle size of LDL was smaller in the high insulin group than in the low insulin group (258 ± 7 vs 265 ± 6 Å, p 〈 0.05). We propose that the changes of lipoprotein lipase and lipoprotein lipase/hepatic lipase ratio cluster with insulin resistance and provide a possible mechanism to explain the lowering of HDL cholesterol and elevation of triglyceride concentrations observed in insulin-resistant subjects. [Diabetologia (1995) 38: 344–350]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Key words Microalbuminuria ; insulin resistance syndrome ; insulin sensitivity ; euglycaemic hyperinsulinaemic clamp.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microalbuminuria has recently been associated with insulin resistance in both insulin-dependent and non-insulin-dependent (NIDDM) diabetes mellitus. To establish whether microalbuminuria in non-diabetic subjects as well is associated with insulin resistance and associated abnormalities in glucose and lipid metabolism, oral glucose tolerance tests were performed with measurement of urinary albumin excretion rate, lipids and lipoproteins in 582 male non-diabetic first-degree relatives of patients with NIDDM. In addition, insulin sensitivity was assessed in 20 of these subjects with the euglycaemic hyperinsulinaemic clamp technique. Abnormal albumin excretion rate (AER), defined as AER 15–200 μg/min, was associated with higher systolic blood pressure (p 〈 0.05), higher fasting glucose values (p 〈 0.05), lower HDL-cholesterol (p 〈 0.05) and lower apolipoprotein A-I (p 〈 0.05) concentrations than observed in subjects with normal AER. The rate of glucose metabolism was lower in subjects with abnormal compared to subjects with normal albumin excretion rate (38.0 ± 2.8 vs 47.3 ± 2.4 μmol · kg lean body mass–1· min–1; p = 0.028). This difference was almost completely accounted for by a reduction in non-oxidative glucose metabolism (17.7 ± 1.9 vs 27.4 ± 2.7 μmol · kg lean body mass–1· min–1; p = 0.010), which correlated inversely with the AER (r = –0.543; p = 0.013). These results suggest that in non-diabetic individuals genetically predisposed to NIDDM, abnormal AER is associated with insulin resistance and abnormalities in glucose and lipid metabolism. [Diabetologia (1995) 38: 363 –369]
    Type of Medium: Electronic Resource
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