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Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 235 records · Page 13Linked to original sources
PubMed1995

Insulin sensitivity and Lp(a) concentrations in normoglycemic men.

OBJECTIVE: Increased lipoprotein(a) [Lp(a)] concentrations have been recognized as a risk factor for coronary heart disease. Little data exists on the relationship of Lp(a) concentrations to insulin resistance. RESEARCH DESIGN AND METHODS: We examined insulin resistance (as determined by the euglycemic clamp) together with indirect calorimetry in relation to Lp(a) concentrations, apolipoprotein(a) [apo(a)] molecular weight, and apo(a) phenotype in 87 normoglycemic men. RESULTS: Lp(a) concentrations were significantly related to total (r = 0.225) and nonoxidative (r = 0.256) whole-body glucose disposal. These results suggest a positive but weak association between insulin sensitivity (restricted to the nonoxidative whole-body glucose disposal) and Lp(a) concentrations. However, after adjustment for apo(a) molecular weight [which accounts for some of the genetic influences on Lp(a) levels], total and nonoxidative body glucose disposal were not significantly related to Lp(a) concentrations. CONCLUSIONS: Normoglycemic insulin-resistant subjects do not have elevated Lp(a) concentrations.

Apolipoproteins↗
PubMed1995

Glucokinase gene variants in subjects with late-onset NIDDM and impaired glucose tolerance.

OBJECTIVE: To investigate the frequency of variants of the glucokinase (GCK) gene in subjects with late-onset non-insulin-dependent diabetes mellitus (NIDDM) and in subjects with late-onset impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: The study population included 36 Finnish patients with late-onset NIDDM who were treated with diet for > 8 years or who were newly diagnosed and 40 subjects with late-onset IGT who had low or normal insulin levels when tested by an oral glucose tolerance test. All exons, exon-intron junctions, and islet and liver promotor regions of the GCK gene were amplified with the polymerase chain reaction and screened for mutations using single-strand conformation polymorphism analysis. RESULTS: A silent third-base substitution (TAC: >TAT) in codon 215 of exon 6 was found in 2.8% of NIDDM patients and in 5.0% of IGT subjects. Polymorphisms were found in islet exon 1 at nucleotide 403 (C-->G) in 16.7% of NIDDM patients and in 17.5% of IGT subjects and in the noncoding region of the islet promotor at nucleotide -30 (G-->A) in 13.9% of NIDDM patients and in 25.0% of IGT subjects. Furthermore, in liver intron 1 a variant (C-->T), 12 base pairs upstream from the splice acceptor site, was found in 5.6% of NIDDM patients and in 7.5% of IGT subjects. CONCLUSIONS: These results indicate that the mutations in the coding region of the GCK gene are not likely to play a major role the pathogenesis of late-onset NIDDM or IGT in the Finnish population.

Diabetes Mellitus, Type 2↗
PubMed1995

Use of clodronate in multiple myeloma.

Multiple myeloma is characterized by bone disease including osteoporosis, osteolytic lesions, pathological fractures and hypercalcaemia leading to pain, immobilization and decrease in the quality of life. Clodronate, a bisphosphonate, has been shown to be effective in the treatment of hypercalcaemia in patients with multiple myeloma. In addition, clodronate reduces the progression of osteolytic lesions and the amount of vertebral fractures and may also relieve pain in these patients. Recent studies suggest that oral clodronate should be considered in the adjunctive treatment of all patients with active multiple myeloma independently of the presence of bone lesions at diagnosis. Due to its safety and efficacy, clodronate seems to have gained an important role in the management of patients with multiple myeloma.

Antimetabolites↗
PubMed1995

The interuncal distance in Alzheimer disease and age-associated memory impairment.

PURPOSE: To examine the value of measurement of the interuncal distance in the diagnosis of mild to moderate Alzheimer disease. METHODS: We measured interuncal distance from coronal MR scans acquired on a 1.5-T imager. We estimated interuncal distance from a total of 141 subjects: 54 patients diagnosed according to the National Institute of Neurological and Communicative Disorders and the Alzheimer's Disease and Related Disorders Association criteria of probable Alzheimer disease, 40 subjects fulfilling the National Institute of Mental Health criteria of age-associated memory impairment, 27 healthy cognitively normal older control subjects, and 20 control subjects younger than 50 years of age. For comparison we normalized interuncal distance for a horizontal line drawn through the inner cranium at the level of the uncus (interuncal distance/intracranial width ratio), for the brain area (interuncal distance/brain area) and for the intracranial area (interuncal distance/intracranial area). RESULTS: The standard interuncal distance and the interuncal distance/intracranial width differed between the young control subjects and the other groups, but did not differ among the control, age-associated memory impairment, and Alzheimer disease groups. The Alzheimer disease group had significantly greater interuncal distance/intracranial area and interuncal distance/brain area compared with age-matched controls. A considerable overlap was found, however, in the values of patients with Alzheimer disease and control subjects. The cutoff point of 30 mm for interuncal distance yielded 37% sensitivity and 72% specificity to distinguish patients with Alzheimer disease from nondemented elderly subjects. Interuncal distance was not significantly related to the clinical severity of Alzheimer disease as assessed by Clinical Dementia Rating Scale and Mini-Mental Status Examination. Instead, there was a strong correlation between standard and normalized interuncal distance and age in the whole study population and in nondemented subjects. CONCLUSIONS: Our results showed that in a series of 54 patients with mild to moderate Alzheimer disease, interuncal distance was not a reliable diagnostic tool. The study also confirmed the strong age dependence for interuncal distance.

Adult↗
PubMed1994

Structure of the human hexokinase II gene.

Mutations in the gene encoding hexokinase II which catalyzes a key step in glycolysis could contribute to the development of peripheral insulin resistance and lead to non-insulin-dependent diabetes mellitus. As a first step towards screening patients for mutations in this gene, we have determined its structure and the sequence of exon-intron junctions. The human HKII gene is composed of 18 exons that span at least 40 kb, and its organization is highly homologous to that of the rat gene. A hexokinase II processed pseudogene was discovered while screening a human genomic library. The coding sequence of this pseudogene is uninterrupted by introns and contains at least one premature stop codon.

Base Sequence↗
PubMed1994

Left ventricular systolic function in middle-aged patients with diabetes mellitus.

In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 +/- 1.1% (mean +/- SEM) in control subjects, 3.1 +/- 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 +/- 1.4% (p < 0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (< 50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p < 0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by < 5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Is there a sex difference in the association of plasma insulin level and insulin sensitivity with serum lipids and lipoproteins?

Previous studies on the relationship between the plasma insulin level, insulin sensitivity (SI), serum lipids, and lipoproteins have been performed predominantly in men. Therefore, we investigated whether there is a sex difference in the association of insulin level during an oral glucose tolerance test and SI with lipids and lipoproteins among normoglycemic men and women aged 53 to 61 years. SI was determined by the minimal model from the frequently sampled intravenous glucose tolerance test (IVGTT). There were no correlations between total cholesterol or low-density lipoprotein (LDL) cholesterol and insulin level or SI. High-density lipoprotein (HDL) cholesterol correlated inversely with fasting insulin (r = -.26, P < .05 in men; r = -.29, P < .01 in women) and 2-hour insulin (r = -.31, P < .01 in men; r = -.39, P < .001 in women) and positively with SI (r = .28, P = .05 in men; r = .43, P < .001 in women). Total and very-low-density lipoprotein (VLDL) triglycerides correlated positively with fasting insulin (r = .43, P < .001 in men; r = .42, P < .001 in women) and 2-hour insulin (r = .50, P < .001 in men; r = .31, P < .01 in women) and inversely with (r = -.49, P < .001 in men; r = -.40, P < .001 in women). In multiple regression analyses including age, body mass index (BMI), waist to hip ratio, 2-hour glucose, fasting or 2-hour insulin, and SI, only BMI was associated with HDL cholesterol level in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

Hearing thresholds in insulin-dependent diabetic patients.

Hearing thresholds were studied in 53 patients with insulin-dependent diabetes mellitus (IDDM) and 42 randomly selected non-diabetic control subjects, aged between 20 and 40 years. The hearing level tended to be worse in diabetic patients than in control subjects, but the differences were statistically significant only at frequencies of 6,000 and 8,000 Hz. Microvascular complications (retinopathy and nephropathy), and the duration of diabetes were associated with the elevated hearing thresholds. In contrast, poor metabolic control (high fasting blood glucose and glycated haemoglobin A1c) was not associated with increased hearing thresholds. The changes caused by diabetic neuropathy appeared simultaneously with microvascular complications and a long duration of the diabetes, and thus a causative role of diabetic neuropathy in the pathogenesis of elevated hearing thresholds remained unsolved. It was concluded that elevated sensorineural hearing thresholds at the frequencies of 6,000 and 8,000 Hz in patients with IDDM are probably caused by the long duration of diabetes and the microvascular complications associated with it.

Adult↗
PubMed1994

Subgroup and cost-benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group.

Osteolytic lesions and pathological fractures are the major problems in the clinical management of multiple myeloma. We previously reported the main results of a randomized, controlled multicentre trial in 350 Finnish patients with multiple myeloma. All patients received standard melphalan-prednisolone treatment and were randomized to receive either clodronate 2.4 g daily or a placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group as in the clodronate group (24.0% v 12.0%, P = 0.026). The purpose of the present study was to investigate factors associated with the progression of osteolytic lesions and to identify subgroups of patients who would benefit most from clodronate treatment. In univariate logistic regression analysis, including treatment (placebo, clodronate), sex, age, pain index, serum calcium and creatinine, myeloma stage, number of osteolytic lesions at baseline, and number of vertebral fractures at baseline as independent variables and the progression of osteolytic lesions as a dependent variable, only the treatment with a placebo was associated with the progression of osteolytic bone lesions. Separate analyses with respect to the progression of osteolytic bone lesions were carried out in the following subgroups: male v female, < or = 64 v > 64 years, stage I v stage II-III myeloma, no osteolytic lesions at baseline versus osteolytic lesions at baseline, no vertebral fractures at baseline versus vertebral fractures at baseline. and a 50% treatment response to cytotoxic drugs versus no treatment response to cytotoxic drugs. The treatment with clodronate delayed the progression of osteolytic lesions similarly in these subgroups, with the exception of a subgroup of patients who did not have a 50% treatment response to cytotoxic drugs. The treatment with clodronate did not significantly increase treatment costs. We conclude that the treatment effect of clodronate seems to be independent of sex and age of the patients, the stage of myeloma, and the severity of bone lesions at diagnosis, but not of treatment response to cytotoxic drugs.

Aged↗
PubMed1994

Myocardial infarct size and mortality in patients with non-insulin-dependent diabetes mellitus.

OBJECTIVES: To study the infarct size and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in non-diabetic subjects with their first acute myocardial infarction. DESIGN: Seven year follow-up study of large representative cohorts of patients with non-insulin-dependent diabetes mellitus and non-diabetic subjects (study 1) and the FINMONICA acute myocardial infarction register study in 1988-89 (study 2). SETTING: Populations of the districts of the Kuopio University Hospital and Turku University Central Hospital (study 1). Populations of Kuopio and North Karelia provinces and Turku/Loimaa area (study 2). SUBJECTS: Study 1: 1059 patients with non-insulin dependent diabetes mellitus and 1373 non-diabetic subjects aged 45-64 years at baseline; during the follow-up 166 patients with non-insulin-dependent diabetes mellitus (91 men and 75 women) and 30 non-diabetic subjects (25 men and five women) were hospitalized for their first acute myocardial infarction. Study 2: 1622 patients aged 25-64 years hospitalized for their first acute myocardial infarction; 144 patients (90 men and 54 women) had non-insulin-dependent diabetes mellitus and 1153 (890 men and 263 women) were non-diabetic. MAIN OUTCOME MEASURES: The infarct size was assessed on the basis of maximum levels of serum cardiac enzymes (studies 1 and 2) and QRS-score (study 1). RESULTS: No differences were found in maximum levels of serum cardiac enzymes between diabetic and non-diabetic patients. Similarly QRS-score gave no suggestion of a difference in infarct size between diabetic and non-diabetic patients. In both studies mortality before hospital admission was similar in diabetic and non-diabetic patients, but mortality within 28 days from hospital admission was twice as high in diabetic patients as in non-diabetic patients. Cardiac failure was the main cause of death significantly more often in diabetic patients than in non-diabetic patients (study 2). CONCLUSIONS: Poorer prognosis of acute myocardial infarction in diabetic patients appears not to be explained by a larger infarct size but probably by adverse effects of the diabetic state itself on myocardial function.

Cause of Death↗
PubMed1994

Subjective memory complaints and personality traits in normal elderly subjects.

OBJECTIVE: To evaluate the relationship between objectively measured memory functions and subjective complaints of memory disturbance and whether subjective complaints are affected by some personality traits or affective states. DESIGN: Cross-sectional two-group comparison. SETTING: The city of Kuopio in Eastern Finland, considered representative of the urban elderly population of Finland. PARTICIPANTS: Originally 403 subjects aged 67-78 years from the random sample and then two matched study groups initially including eighteen subjects but only ten in the final analysis. MEASUREMENTS: Screening and follow-up examinations of subjects with and without subjective memory complaints: (1) Memory functions: Benton's visual retention test and the paired-associated learning subtest of Wechsler Memory Scale. (2) Memory complaints: Memory Complaint Questionnaire. (3) Personality traits and affective state: Two subscales from Minnesota Multiphasic Personality Inventory and Geriatric Depression Scale. RESULTS: Complaints of memory loss did not correlate with the actual memory performance in the tests. However, those subjects who most emphatically complained of memory disturbance had greater tendencies toward somatic complaining, higher feelings of anxiety about their physical health, and more negative feelings of their own competence and capabilities than those who did not complain of memory deterioration associated with aging. CONCLUSIONS: The study suggests that subjective feelings of memory impairment are more closely associated with personality traits than with actual memory performance in normal elderly people.

Affect↗
PubMed1994

Femoropopliteal angioplasty in patients with claudication: primary and secondary patency in 140 limbs with 1-3-year follow-up.

PURPOSE: To determine the usefulness of percutaneous transluminal angioplasty in the femoropopliteal arteries in patients with claudication. MATERIALS AND METHODS: In a prospective study of 106 claudicants (71 men and 35 women, aged 41-90 years [mean, 67 years]), a total of 208 lesions in 140 limbs were treated. The patients were followed up for 12-36 months. The patency rates were based on determination of the ankle-brachial index. RESULTS: The hemodynamic success rate for all the treated limbs was 89%, 99% for femoropopliteal stenoses (n = 71) and 80% for femoropopliteal occlusions (n = 69). In multiple logistic regression analysis, a smaller number of diseased vessels (one to two vs three to seven) and milder lesion severity (stenosis vs occlusion) correlated favorably with early success. Survival analysis with the Kaplan-Meier method according to established criteria revealed 1-, 2-, and 3-year primary patency rates of 47% (27 of 57 limbs), 41% (14 of 34 limbs), and 43% (three of seven limbs), respectively. CONCLUSION: In selected cases, good primary success and acceptable long-term results can be achieved with femoropopliteal angioplasty in claudicants.

Adult↗
PubMed1994

Lack of association between sex hormones and Lp(a) concentrations in American and Finnish men.

Sex hormones may play a role in the determination of cardiovascular disease. Recently lipoprotein(a) (Lp[a]) has been recognized as a risk factor for coronary heart disease. Estrogens and anabolic steroids have been reported to alter Lp(a) levels, yet no data are available on the association between in vivo concentrations of sex hormones and Lp(a) concentrations. We examined the possible associations of sex hormone-binding globulin, total and free testosterone, estradiol, and dehydroepiandrosterone sulfate to Lp(a) concentrations in men in two population-based studies (San Antonio Heart Study [n = 178] and a Finnish study on the association between insulin resistance and atherosclerosis [n = 87]). In neither study were sex hormones significantly related to Lp(a) concentrations. In addition, Lp(a) was significantly related to apolipoprotein(a) molecular weight (which was measured in the Finnish study only). These results were unchanged when Lp(a) concentrations were adjusted for apolipoprotein(a) molecular weight (a strong correlate of Lp[a] concentrations). We conclude that in vivo concentrations of sex hormones are unlikely to be associated with Lp(a) concentrations in men.

Adult↗
PubMed1994

Hyperinsulinemia predicts multiple atherogenic changes in lipoproteins in elderly subjects.

Several studies have shown that hyperinsulinemia and insulin resistance are associated with high triglyceride and low high-density lipoprotein (HDL) cholesterol levels. However, previous studies have been cross-sectional, and thus the presence of hyperinsulinemia or insulin resistance could be a consequence of the underlying lipid disorder instead of its cause. Therefore, we examined the relation of fasting insulin level measured in a cross-sectional study in nondiabetic subjects 65 to 74 years old (n = 881) to the risk of developing lipid disorders 3.5 years later. The incidence of the following lipid abnormalities was calculated: hypertriglyceridemia (n = 49/732, incident cases/subjects free of the particular disorder at baseline), high low-density lipoprotein (LDL) cholesterol level (n = 43/696), low HDL cholesterol level (n = 33/708), high apolipoprotein (apo) B level (n = 72/699), low apoAI level (n = 47/711), low serum LDL cholesterol/serum apoB ratio (n = 55/685), and low serum HDL cholesterol/serum apoAI ratio (n = 48/707). Baseline insulin level was not significantly associated with the development of high LDL cholesterol or low HDL cholesterol levels. Baseline insulin was associated with the development of hypertriglyceridemia (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12 to 2.40; P = .011), high apoB (OR, 1.54; 95% CI, 1.13 to 2.10; P = .006), low apoAI (OR, 1.72; 95% CI, 1.22 to 2.42; P = .002), low LDL cholesterol/apoB ratio (OR, 1.99; 95% CI, 1.36 to 2.90; P < .001), and low HDL cholesterol/apoAI ratio (OR, 1.93; 95% CI, 1.34 to 2.79; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Insulin sensitivity is not an independent determinant of plasma plasminogen activator inhibitor-1 activity.

It recently has been hypothesized that increased plasma plasminogen activator inhibitor-1 (PAI-1) activity could be a possible link between insulin resistance and coronary heart disease. However, it is not known whether insulin sensitivity per se is a determinant of plasma PAI-1 activity or whether other intermediates could explain this association. We investigated the relationship between plasma PAI-1 activity and insulin sensitivity, obesity, distribution of body fat, blood pressure, plasma insulin concentration, and serum lipid levels in normoglycemic men (n = 61) and women (n = 77) 53 to 61 years old who participated in a previous population-based study. Insulin sensitivity was estimated by the minimal model from a frequently sampled intravenous glucose tolerance test. In univariate analyses, PAI-1 correlated positively with body mass index, waist-to-hip ratio (WHR), fasting and 2-hour insulin levels, and triglyceride level in both men and women. Furthermore, in women PAI-1 correlated inversely with high-density lipoprotein (HDL) cholesterol level. There was an inverse relationship between PAI-1 and insulin sensitivity (r = -.39, P < .01 in men; r = -.38, P < .001 in women). In multivariate analyses in men, insulin sensitivity failed to show any significant association with PAI-1. In contrast, triglyceride level and body mass index were independently associated with PAI-1. Also in women, insulin sensitivity was not independently associated with PAI-1. In women, WHR and HDL cholesterol concentration or WHR and 2-hour insulin concentration were independently related to PAI-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1994

Non-insulin-dependent diabetes and its metabolic control are important predictors of stroke in elderly subjects.

BACKGROUND AND PURPOSE: Non-insulin-dependent diabetes mellitus (NIDDM) is a major risk factor for stroke in the middle-aged population, but few prospective population-based studies are available in the elderly. Moreover, the importance of metabolic control and the duration of diabetes in diabetic subjects has remained controversial. There are no previous studies on association of insulin with the risk of stroke. The present study examined whether NIDDM, its metabolic control and duration, and insulin level predict stroke. METHODS: We measured cardiovascular risk factors including glucose tolerance, plasma insulin, and glycosylated hemoglobin A1c in a Finnish cohort of 1298 subjects aged 65 to 74 years and investigated the impact of these risk factors on the incidence of both fatal and nonfatal stroke during 3.5 years of follow-up. RESULTS: Of 1298 subjects participating in the baseline study, 1069 did not have diabetes and 229 had NIDDM. During the 3.5-year follow-up, 3.4% (n = 36) of nondiabetic subjects and 6.1% (n = 14) of NIDDM subjects had a nonfatal or fatal stroke. The incidence of stroke was significantly higher in diabetic women compared with nondiabetic women (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.65 to 3.06). In contrast, the risk of stroke was not significantly higher in diabetic men than in nondiabetic men (OR, 1.36; 95% CI, 0.44 to 4.18). In multivariate logistic regression analyses including all study subjects, fasting and 2-hour glucose (P < .01 and P < .05, respectively), glycosylated hemoglobin A1c (P < .01), atrial fibrillation (P < .05), hypertension (P < .05), and previous stroke (P < .01) predicted stroke events. In diabetic subjects, fasting and 2-hour glucose (P < .01 and P < .05, respectively), glycosylated hemoglobin A1c (P < .05), the duration of diabetes (P < .05), and atrial fibrillation (P < .05) were the baseline variables predicting stroke events. Finally, fasting insulin (P < .05), hypertension (P < .05), and previous stroke (P < .01) were associated with stroke incidence in nondiabetic subjects. CONCLUSIONS: Our 3.5-year follow-up study provides evidence that NIDDM, its metabolic control, and the duration of diabetes are important predictors of stroke in elderly subjects, particularly in women. Moreover, fasting insulin level appears to be a risk factor for stroke in elderly nondiabetic subjects.

Aged↗
PubMed1994

Insulin receptor substrate-1 variants in non-insulin-dependent diabetes.

Insulin receptor substrate-1 (IRS-1) plays an important role in insulin-stimulated signaling mechanisms. Therefore, we investigated the frequency and clinical significance of variants in the coding region of this gene in patients with non-insulin-dependent diabetes (NIDDM). Initial screening included a population-based sample of 40 Finnish patients with typical NIDDM. Applying single strand conformation polymorphism analysis the following amino acid substitutions were found among the 40 NIDDM patients: Gly818-Arg, Ser892Gly, and Gly971Arg. The first two variants have not been previously reported. Additional samples of 72 patients with NIDDM and 104 healthy control subjects with completely normal oral glucose tolerance test and a negative family history of diabetes were screened. The most common polymorphism was the Gly971Arg substitution which was found in 11 (9.8%) of 112 NIDDM patients and in 9 (8.7%) of 104 control subjects. The Gly818Arg substitution was found in 2 (1.8%) of NIDDM patients and in 2 (1.9%) of control subjects, and the Ser892Gly substitution was found in 3 (2.7%) NIDDM patients and in 1 (1.0%) control subject. The Gly971Arg substitution was not associated with an impairment in insulin secretion capacity (estimated by insulin responses in an oral glucose tolerance test or by the hyperglycemic clamp) or insulin action (estimated by the euglycemic clamp). Of the three amino acid substitutions observed Ser892Gly is the most interesting one since it abolishes one of the potential serine phosphorylation sites (SPGE) which is located immediately NH2-terminal to the only SH2 binding site of growth factor receptor-bound protein (GRB2), and thus could potentially influence some aspects of signal transduction and metabolic response to insulin.

Aged↗