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PubMed1994

Contribution of glycaemic control, endogenous lipoproteins and cholesteryl ester transfer protein to accelerated cholesteryl ester transfer in IDDM.

In an earlier study we demonstrated that the transfer of cholesteryl ester (CET) estimated as the net mass of CE lost from HDL to the apoB-containing lipoproteins (VLDL + LDL) during incubation of plasma is accelerated in normolipidaemic patients with insulin-dependent diabetes mellitus (IDDM). Recombination experiments with isolated lipoprotein fractions employing this same mass transfer assay indicated that this disturbance resulted from dysfunction of VLDL and not from changes in the activity of CE transfer protein (CETP). In this study, we sought first to determine whether CET estimated with an isotopic method that measures the transfer of radiolabelled CE from exogenous HDL from non-diabetic controls to endogenous VLDL + LDL was also increased in IDDM and, if so, the extent to which this disturbance was affected by glycaemic control, VLDL and CETP. As observed with the mass transfer assay, the rate of transfer of the HDL-CE label to VLDL + LDL was also significantly accelerated in IDDM plasma (IDDM: k = 0.256 +/- 0.07; control: k = 0.092 +/- 0.05; mean +/- SD; P < 0.001). Fasting glucose and fructosamine correlated with both isotopic transfer (k) (r = 0.54, P = 0.009; r = 0.57, P = 0.005, respectively) and the mass of CE transferred at 2 h (r = 0.55, P = 0.006; r = 0.59, P = 0.004, respectively). Recombination experiments revealed that isotopic CET was accelerated when: (a) IDDM VLDL were combined with controls HDL and d > 1.21 fractions; and (b) IDDM d > 1.21 plasma fractions containing CETP were combined with controls VLDL + LDL and HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Monitoring the progress of non-enzymatic glycation in vitro.

The progress of in vitro non-enzymatic glycation of bovine serum albumin was followed by using 14C-glucose and a nitroblue tetrazolium assay, absorption and fluorescence spectroscopy, SDS gel electrophoresis and protease digestion. The number of adducts detectable using both 14C-tracers and a fructosamine assay remained low at physiological glucose concentrations, fewer than five adducts being detectable. When glucose concentrations > 1.0 M were used the number of adducts was found to greatly exceed the number of lysyl residues available in BSA, indicative of cross-linking between Maillard products. Incubation of BSA with glucose concentrations of up to 160 mM for one month produced no observable increase in molecular weight by SDS gel electrophoresis, showing that at physiological glucose concentrations, increases in molecular weight were minimal for short incubation periods, any marked changes (indicated by non-penetration of the 7.5% SDS gel) requiring nine months incubation with > or = 20 mM glucose. Increases in absorption were proportional to both the glucose concentration and the incubation time. Several absorption peaks, at 370, 488 and 554 nm, were consistent in appearance throughout the course of each incubation. Fluorescence spectroscopy of the modified proteins showed a disappearance of the fluorescence associated with peptide bonds and aromatic residues and the appearance of a broad peak at longer wavelengths due to the wide range of absorptive/fluorescent wavelengths of the developing Maillard products. Protease digestion gave similar patterns with non-glycated and glycated protein, suggesting that glycation did not block digestion sites, and that partial digestion did not cause significant further exposure of susceptible sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrates↗
PubMed1998

Longissimus dorsi muscle diameter, backfat thickness, body condition scores and skinfold values related to metabolic and endocrine traits in lactating dairy cows fed crystalline fat or free fatty acids.

An experiment was performed using 18 dairy cows with > or = 2 lactations from parturition until week 20 of lactation to investigate the effects of feeding rumen-protected crystalline fat (group A) or free fatty acids (group B) compared with a control group not fed supplemental fat or fatty acids (group C). The feeding effects studied were those on milk yield and composition, body weight (BW), body conditions scores (BCS), skinfold values (a measure of subcutaneous fat tissue thickness), backfat thickness and longissimus dorsi muscle diameter (measured by ultrasound), as well as on blood plasma metabolic and endocrine traits. Fat and fatty-acid feeding reduced roughage intake. Net energy and protein balances during the first week of lactation were negative. Milk yield was similar in all groups, but concentrations of milk fat were reduced in group B and of milk protein in groups A and B. BW, BCS, skinfold value, backfat thickness and longissimus dorsi muscle diameter similarly decreased in all groups until weeks 8-12. Concentrations of glucose and fructosamine decreased transiently during early lactation, whereas levels of beta-hydroxybutyrate, urea, total protein and albumin increased reversibly and similarly in all groups. Concentrations of creatinine decreased similarly in all groups until week 4 and those of nonesterified fatty acids until week 12. Triglyceride concentrations increased continuously until week 18, whereas concentrations of phospholipid and cholesterol increased until week 10 and then remained elevated. Triglyceride, phospholipid and cholesterol concentrations were higher in group B than in groups A and C throughout the experiment. Concentrations of insulin, insulin-like growth factor-1, thyroxine and 3,5,3'-triiodothyronine started to increase after the first 6-8 weeks of lactation, while those of growth hormone were transiently low in week 16. None of the hormones exhibited group differences. In this study rumen-protected fat or fatty-acid supplementation failed to improve the energy and protein balances during early lactation and did not affect milk yield, likely due to decreased roughage intake. BCS, skinfold values and backfat ultrasound measurements of subcutaneous adipose tissue mass and of longissimus dorsi muscle diameter indicated mobilization of fat tissue and protein mobilization in early lactation and were mirrored by typical changes of metabolic and endocrine traits.

Adipose Tissue↗
PubMed1997

Tropical calcific pancreatitis and fibrocalculus pancreatic diabetes in Bangladesh.

The relationship between tropical calcific pancreatitis (TCP) and fibrocalculus pancreatic diabetes (FCPD) is still unclear. The clinical, biochemical and radiological data of age-matched TCP and FCPD subjects have been briefly discussed in the present review. Fibrocalculus pancreatic diabetes patients present with a significantly lower BMI compared with TCP patients. Analysis of the family history reveals that some kind of environmental factors seem to play a predominant role in the development of diabetes in FCPD patients, although these factors remain to be identified. Both TCP and FCPD patients predominantly come from a rural background. Fasting and 2 h blood glucose values as well as fructosamine levels in FCPD patients are approximately four-times higher than those of TCP patients. Measurements of early renal haemodynamic and microvascular changes (glomerular filtration rate, kidney size, microalbuminuria and microtransferrinuria) indicate an early renal involvement in FCPD patients. Tropical calcific pancreatitis subjects have approximately twice as high fasting C-peptide values compared with FCPD patients. Findings of single stranded DNA measurements suggest the involvement of oxidative damage in FCPD patients. Ketosis resistance is the most conspicuous clinical feature in the FCPD group and this relative absence of ketosis is probably due to a defect in the ketone body synthesis pathway and/or in the regulation of counterbalancing hormones. Endoscopic retrograde pancreatography findings of TCP and FCPD patients suggest that FCPD should not be considered only as a form of secondary diabetes consequent to generalized pancreatic damage in TCP.

Adolescent↗
PubMed1994

Red blood cell sorbitol in diabetic children.

When red blood cells (RBC) were incubated with various concentrations of glucose, the RBC sorbitol level increased in a concentration-dependent manner. The elevated RBC sorbitol level was not reduced by further incubation in a glucose-free medium. In both diabetic and non-diabetic children, an increase of RBC sorbitol levels occurred in the oral glucose tolerance test and the return to baseline was delayed in diabetics compared with non-diabetics. In the majority of diabetics (87%), RBC sorbitol levels exceeded the upper limit of the normal range, which was arbitrarily determined as the mean + 2 s.d., in healthy non-diabetic children and adults. A good correlation was observed between RBC sorbitol levels and plasma glucose levels (r = 0.644). In both diabetics and non-diabetics, no correlation was observed between RBC sorbitol levels and age, and in diabetics the RBC sorbitol level was not related to the duration of disease. A good correlation was observed between RBC sorbitol levels, and hemoglobin Alc (HbAlc) or fructosamine levels in diabetic children.

Adolescent↗
PubMed1992

Lipoprotein(a) concentration in diabetes: relationship to proteinuria and diabetes control.

Diabetic patients are at increased risk of cardiovascular disease, particularly when proteinuria is present. Lipoprotein(a)[Lp(a)] levels were assessed in 37 patients with insulin dependent (IDDM) and in 75 patients with non-insulin dependent (NIDDM) diabetes who showed varying degrees of proteinuria and glycaemic control. Median Lp(a) in 112 diabetic patients was significantly greater than in 116 healthy controls (113 vs 48 mg/L; p less than 0.01). 86 of the patients had first morning urine albumin concentration less than 30 mg/L (normoalbuminuria = NA), 16 patients 30-200 mg/L (microalbuminuria = MA) and ten patients greater than 200 mg/L (albuminuria = ALB). There was no significant difference in median Lp(a) concentration between the three groups (NA = 108, MA = 163, ALB = 98 mg/L; p greater than 0.5). No significant difference in median Lp(a) or NIDDM treated with oral agents and/or diet (120, 98, 115 mg/L respectively; p greater than 0.7). When the 86 NA patients were divided on the basis of median fructosamine concentration (357 mumol/L), no significant difference was found in median Lp(a) levels between those grouped below or above this median (98 mg/L vs 118 mg/L; p greater than 0.5). Across all diabetics studied there was no significant correlation present between Lp(a) and urinary protein or glycaemic control. These cross-sectional results suggest that median Lp(a) concentration is increased in both IDDM and NIDDM patients, but this increase is not related to the degree of proteinuria or short-term glycaemic control.

Adolescent↗
PubMed2006

Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept study.

AIM: This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. METHODS: Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 +/- 6.6 years, body mass index 32.7 +/- 4.2 kg/m(2), glycosylated haemoglobin (HbA1c) 8.4 +/- 0.8% (mean +/- s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. RESULTS: INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (-2.7 vs. -3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (-1.23 vs. -1.05%), body weight (-1.9 vs. -2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (-1.15 micromol/l; p < 0.001) but not with GLA [-0.52 micromol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. CONCLUSIONS: In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies.

Administration, Inhalation↗
PubMedDate not supplied

Keratoconjunctival effects of diabetes mellitus in dogs.

OBJECTIVES: To compare Schirmer tear test (STT) values, corneal sensitivity, tear film break up times (TFBUTs), and tear glucose concentrations in relation to conjunctival microflora, and conjunctival cytologic and histologic findings among diabetic cataractous, nondiabetic cataractous, and nondiabetic noncataractous dogs. Procedures Fifteen dogs in each category underwent neuro-ophthalmic examination; aerobic, anaerobic and fungal conjunctival cultures; assessment of corneal touch threshold (CTT), STT, tear glucose, TFBUT; and conjunctival cytology and histology (in certain cases only). Degree of cataract and uveitis were critically graded. Glycemic control was estimated using serum fructosamine and glycosylated hemoglobin. RESULTS: STT values were significantly lower in diabetic cataractous than nondiabetic noncataractous dogs. CTT of diabetic cataractous dogs was significantly lower than that of nondiabetic noncataractous dogs. Mean TFBUTs were significantly less in diabetic cataractous dogs than nondiabetic cataractous and nondiabetic noncataractous dogs. Tear glucose concentrations were significantly higher in diabetic cataractous dogs than nondiabetic cataractous and nondiabetic noncataractous dogs. Conjunctival microbial isolates did not differ among groups. There were no significant differences in degree of cataract or uveitis between diabetic cataractous and nondiabetic cataractous groups. There was mild submucosal inflammatory infiltrate in conjunctival specimens from diabetic dogs. Conjunctival epithelial dysplasia and/or squamous metaplasia was/were detected in conjunctival biopsies of 5/7 diabetic dogs. Reductions in conjunctival goblet cell (GC) densities were noted in 4/7 diabetic dogs; there were no significant differences in mean GC densities among the three groups. CONCLUSIONS: Diabetic cataractous dogs have significantly altered keratoconjunctival characteristics compared to nondiabetic cataractous and nondiabetic noncataractous dogs.

Animals↗
PubMed1988

Alpha glucosidase inhibition in the treatment of non-insulin-dependent diabetes mellitus.

Two studies of the new alpha-glucosidase inhibitor, miglitol, in patients with non-insulin-dependent diabetes mellitus (NIDDM) are reported. In the first, 13 patients, poorly controlled on sulphonylureas, received miglitol 50mg three times daily for 4 weeks. Post-prandial blood glucose was reduced after breakfast, lunch, and tea compared with placebo (p less than 0.05-0.01) but there was no improvement in fasting blood glucose, serum fructosamine or haemoglobin A1. In a dose-response study the effect of a single dose of miglitol (0,50,100,150 or 200mg) on post-prandial glycaemia after a test breakfast was assessed in 20 patients with mean +/- SEM fasting blood glucose 9.9 +/- 0.4 mmol/l. With 50mg miglitol, there was a significant reduction in blood glucose from 30 to 120 min post-prandially compared with placebo. Increasing doses of miglitol further depressed the post-prandial rise in blood glucose and with 200mg there was no significant change from fasting levels. Side-effects were limited to flatus and loose stools particularly with the higher doses but were not severe. Miglitol effectively reduces post-prandial blood glucose rise in NIDDM with as little as 50mg but there is considerable individual variation. Larger doses may be necessary in patients already poorly controlled on sulphonylureas.

1-Deoxynojirimycin↗
PubMed1988

The fluorescence of serum proteins in diabetic patients with and without retinopathy.

Non-enzymatic glycosylation of long-lived proteins results in a characteristic fluorescence, known as protein 'browning'. The degree of fluorescence of skin collagen correlates with retinopathy in diabetes. We have therefore measured the fluorescence of serum albumin and IgG by a sensitive HPLC technique in 69 diabetic patients, 38 with retinopathy and 31 without complications, and in 26 age-matched controls. The fluorescence of the IgG fraction, calculated as the ratio of fluorescence (excitation 360 nm, emission 454 nm) to optical density (280 nm), was elevated in diabetic patients with retinopathy (1.5 +/- 0.5) compared with those without retinopathy (1.1 +/- 0.2, p less than 0.005) and control subjects (1.1 +/- 0.2, p less than 0.005). The fluorescence ratio for the albumin fraction was increased in all diabetic patients (11.2 +/- 2.7) compared with control subjects (8.9 +/- 1.5, p less than 0.001). There was no significant difference in the fluorescence ratios of albumin in those with and without retinopathy. The fluorescence of serum albumin and IgG were not significantly correlated with serum protein glycosylation measured by the fructosamine method.

Biomarkers↗
PubMed1989

The effects of metformin on adipocyte insulin action and metabolic control in obese subjects with type 2 diabetes.

To investigate the mechanisms of action of metformin, insulin receptor binding and the activity of several insulin-controlled metabolic pathways were measured in adipocytes taken from 10 obese Type 2 diabetic patients treated for 4 weeks with either metformin (0.5 g x 3 daily) or matching placebo using a double-blind crossover design. Metformin therapy was associated with a significant fall in serum fructosamine levels (3.1 +/- 0.4 vs 2.8 +/- 0.4 mmol l-1, p less than 0.02) as well as fasting (10.8 +/- 2.4 vs 9.4 +/- 2.1 mmol l-1) and daytime (11.5 +/- 2.4 vs 10.0 +/- 2.2 mmol l-1) plasma glucose concentrations (p less than 0.05). Fasting and postprandial plasma levels of C-peptide and insulin were unchanged. While fasting plasma lactate concentrations remained unaltered after metformin, a rise was noted in response to meals (from 1.4 +/- 0.1 to 1.8 +/- 0.2 mmol l-1, p less than 0.05). Adipocyte insulin receptor binding was unaffected by drug treatment. Moreover, no insulin-like effects or post-binding potentiation of insulin action could be found on adipocyte glucose transport, glucose oxidation, lipogenesis, glycolysis or antilipolysis. A complementary in vitro study using adipocytes from non-obese healthy volunteers failed to show any direct effect of metformin on adipocyte insulin binding or glucose transport and metabolism, at media drug concentrations corresponding to therapeutic plasma levels.

Adipose Tissue↗
PubMed1989

Efficacy and acceptance of two intensified conventional insulin therapy regimens: a long-term cross-over comparison.

The efficacy and acceptability of multiple daily insulin injections (three preprandial injections of short-acting insulin (NovoPen) plus once daily extended-acting insulin) were compared with those of twice daily injections of short- and intermediate-acting insulin. Sixteen Type 1 diabetic patients participated in a cross-over study (6-month treatment periods). Total areas under 24-h plasma free insulin curves, assessed at the end of each study period, were not significantly different, but a greater area under this curve was found for the pen-injector regimen from 1200 to 1600 h (150 +/- 15 (SE) vs 106 +/- 7 mU l-1 h, p less than 0.01). Home blood glucose profiles showed significantly lower values with pen-injector therapy after lunch (7.1 +/- 0.6 vs 8.4 +/- 0.4 mmol l-1, p = 0.05) and before and after dinner (6.4 +/- 0.6 vs 8.8 +/- 0.5 mmol l-1, p less than 0.005, and 7.5 +/- 0.7 vs 9.4 +/- 1.1 mmol l-1, p less than 0.05). Mean daily blood glucose concentration was also lower (7.1 +/- 0.4 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05). HbA1, fructosamine, hypoglycaemic reactions, and body weight were not significantly different. Thirteen patients decided to continue with pen-injector therapy at the end of the study.

Adult↗
PubMed1990

The necessity of achieving good laboratory performance.

The results of clinical biochemistry tests are used in the diagnosis of diabetes mellitus by comparing them with reference values or agreed international criteria. Low analytical imprecision is required so that reference values are not unduly widened by analytical variability. Most laboratory test results are used in monitoring. Low analytical imprecision is required so that changes seen in sequential results reflect stability, amelioration or deterioration, not simply analytical variability. Analytical bias should be absent so that results are (1) comparable in individuals over time as methods evolve and instrumentation changes, (2) equivalent over locale since tests may be done in practitioners' surgeries, outpatient clinics, and laboratories, and (3) able to be interpreted against the fixed criteria. A plethora of strategies have been proposed to set numerical desirable standards of performance, these being termed analytical goals, including use of reference values, opinions of clinicians, state of the art, the views of experts, and data on biological variation. Use of data on within-subject biological variation is currently considered the best approach. A generally applicable goal is that the total error should be less than one-half of the within-subject biological variation. Achievement of this adds about 10% through analytical variability to the true test variability. Analytical goals (CV, %) for glucose, fructosamine, urinary albumin, and haemoglobin A1 assays are 2.2, 2.1, 18, and 3.3%, respectively. These goals are targets worthy of attainment, not inflexible criteria of acceptance or rejection of methods.

Albuminuria↗
PubMed1992

Quality of life in young adults with type 1 diabetes in relation to demographic and disease variables.

Sixty-nine young adults (mean age 21 (range 15-25) years) with Type 1 diabetes completed measures of diabetes knowledge and quality of life. Factor analysis of the quality of life scale resulted in the identification of three subscales (social relationships, diabetes concerns, and impact). There was no relation between any of the quality of life subscales with knowledge, or with multiple versus twice-daily insulin injection regimens. Higher self-rated diabetes satisfaction was related to lower fructosamine levels and better clinic attendance (p less than 0.05). Females reported a more negative impact of diabetes on their lives compared with males (p less than 0.05).

Adult↗
PubMed1994

Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C.

Low ascorbate concentrations in diabetes may be secondary to inadequate dietary vitamin C intake or may relate to the varied metabolic roles of the vitamin. To determine whether inadequate dietary intake is a factor we calculated daily vitamin C intakes using both a vitamin C questionnaire and a 4-day food diary in a group of 30 patients with Type 2 diabetes (mean age 68.8 +/- 6.9 yr, 17M/13F) and in 30 community controls (mean age 68.0 +/- 5.5 yr, 12M/18F)). Measures of plasma glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were obtained from 20 subjects in each group. There was no significant difference in daily vitamin C intake between the two groups using both methods: food diary, 61.4 +/- 28.3 (patients) vs 69.5 +/- 33.4 (controls) mg; questionnaire, 54.0 +/- 28.9 (patients) vs 65.0 +/- 30.9 (controls) mg. Vitamin C intake derived from both methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 +/- 19.1 mumol l-1) and dehydroascorbate (27.6 +/- 6.4 mumol l-1) levels were significantly lower in patients vs in controls (68.8 +/- 36.0 and 31.8 +/- 4.8 mumol l-1, respectively), p < 0.0001 and p < 0.01. Plasma ascorbate levels were significantly correlated with vitamin C intake derived from the food diary (p < 0.01) and questionnaire (p < 0.01) methods in the diabetic group only. Low ascorbate levels in diabetes appears to be a consequence of the disease itself and not due to inadequate dietary intake of vitamin C. A short vitamin C questionnaire is a convenient and reliable estimate of vitamin C intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Diabetes in the elderly.

Diabetes affects at least 20% of the population over the age of 65. Half of these patients are unaware that they have the disease. Diabetes in middle-aged subjects is characterized by an impairment in glucose induced insulin release, increased fasting hepatic glucose output and resistance to insulin mediated glucose disposal. In contrast, diabetes in the elderly is primarily associated with insulin deficiency. The presentation of diabetes in the aged is often non-specific. The elderly have an increased frequency of complications from diabetes. They are particularly susceptible to hypoglycaemia, because of reduced awareness of hypoglycaemic warning symptoms and altered release of counterregulatory hormones. Although no data are yet available from randomized controlled trials, there is abundant epidemiological evidence to suggest that adequate control of blood glucose can be expected to reduce the risk of long-term complications. A team approach is ideal for the management of the elderly patient with diabetes. Little data is available on which to base a diet and exercise prescription for elderly patients. Gliclazide appears to be the sulphonylurea of choice in the aged because it is associated with a lower frequency of hypoglycaemic reactions. Urine glucose testing is unreliable, and capillary glucose monitoring is preferred. Fructosamine may prove to be superior to haemoglobin A1C for monitoring long-term control.

Aged↗
PubMed1995

Marked hyperinsulinaemia in postmenopausal, healthy Indian (Asian) women.

The effect of the menopause on insulin metabolism has not received specific attention in populations prone to non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). Insignificant or slight alterations in insulin levels have been reported in postmenopausal women of mainly European ancestry. We thus report on the results of a cross-sectional study on the correlates of fasting insulin levels in 177 healthy, Indian nurses aged between 25 and 55 years. Fasting insulin concentration was markedly higher in the 75 postmenopausal subjects (23.9 mU I-1) than in the 102 premenopausal women (11.7 mU I-1 (p < 0.0001). Forty-three (57%) of the postmenopausal subjects had insulin values more than 20 mU I-1 (the upper normal limit). Stepwise regression analysis on the entire group revealed menopause (p < 0.0001), waist:hip ratio (p = 0.0001), apolipoprotein E genotype (p = 0.002), and the testosterone: sex hormone binding globulin ratio (p = 0.0002) as statistically significant, independent predictors of log insulin levels. Age did not account for the difference between premenopausal and postmenopausal subjects. The apolipoprotein E genotype emerged as a significant correlate of insulin levels, only in postmenopausal women: epsilon 3/3, 26.3 mU I-1; epsilon 3/4, 51.8 mU I-1 (p = 0.0007). Hyperinsulinaemic postmenopausal subjects had higher fasting glucose levels than normoinsulinemic nurses (p = 0.03), but glycosylated haemoglobin and fructosamine values were all within the normal range. Thus fasting hyperinsulinaemia was marked and common among a group of healthy, postmenopausal Indian nurses below the age of 55 years, suggesting that the menopausal transition may permit or provoke insulin resistance in this susceptible population.

Adult↗
PubMed2006

Optimal timing of injection of once-daily insulin glargine in people with Type 1 diabetes using insulin lispro at meal-times.

AIMS: To compare blood glucose control when insulin glargine is given at lunch-time, dinner-time, and bed-time in people with Type 1 diabetes using insulin lispro at meal-times. METHODS: In this 16-week, three-way, cross-over study, 23 people with Type 1 diabetes were randomized to insulin glargine injection at lunch-time (L) [mean 12.37 +/- 00.34 (+/- sd) h], dinner-time (D) (18.12 +/- 00.40 h), or bed-time (B) (22.29 +/- 00.40 h), each plus meal-time insulin lispro. Each 4-week treatment period concluded with a 24-h inpatient metabolic profile. RESULTS: Insulin doses, HbA(1c), and fructosamine concentration did not differ between treatment periods. Pre-breakfast self-monitored blood glucose (SMBG) concentration was higher with injection of glargine at lunch-time than at other times [L: 9.2 +/- 0.3 (+/- se) vs. D: 8.2 +/- 0.3 or B: 8.0 +/- 0.3 mmol/l, P = 0.016], as probably was pre-lunch SMBG (L: 8.6 +/- 0.7 vs. D: 6.4 +/- 0.7 or B: 6.4 +/- 0.8 mmol/l, P = 0.051). Pre-dinner SMBG level was higher with dinner-time glargine than other injection times (D: 9.4 +/- 0.9 vs. L: 4.9 +/- 0.9 or B: 7.4 +/- 1.1 mmol/l, P = 0.007). For 22.00 to 02.00 h, mean inpatient plasma glucose concentration was higher with injection of glargine at bed-time than other times (B: 9.1 +/- 0.6 vs. L: 7.8 +/- 0.6 or D: 6.7 +/- 0.6 mmol/l, P = 0.023). Plasma free insulin concentration was lower at the end of the afternoon with dinner-time glargine than other injection times (D: 11.5 +/- 1.4 vs. L: 20.2 +/- 1.3 or B: 16.5 +/- 1.3 mU/l, P < 0.001). Frequency of hypoglycaemia was not different, but timing of hypoglycaemia differed between treatment periods. CONCLUSIONS: Blood glucose levels rise around the time of injection of insulin glargine whether given at lunch-time, dinner-time or bed-time. Bed-time injection leads to hyperglycaemia in the early part of the night which is improved by giving insulin glargine at lunch-time or dinner-time.

Adolescent↗