Variations Of Glycemia Research Articles

Glycemic profile and effectiveness and safety of insulin therapy in septic patients. Is the blood glucose level sufficient?

Hyperglycemia in sepsis is managed by intensive insulin therapy, which can cause hypoglycemia. The aim of the study was to evaluate the glycemic profile as well as safety and effectiveness of a nurse-controlled insulin therapy protocol in patients with severe sepsis and septic shock. The study included 16 septic patients who died (nonsurvivors) and 61 septic patients who survived. Glycemia was measured every 4 h, and the dose of insulin infusion was adjusted to maintain glycemia of 4.4 mmol/l to 8.3 mmol/l. We analyzed glycemia levels and daily variations, insulin dose, episodes of hypo- and hyperglycemia. Nonsurvivors and survivors had similar mean glycemia levels (7.38 vs. 7.08 mmol/l; p = 0.20) and insulin requirements (median [Me] = 26.9 vs. 23.9 units/d; p = 0.22; Me = 1.7 vs. 1.4 units/h; p = 0.25). Daily glycemia variation (Me = 4.81 vs. 3.03 mmol/l; p <0.001), episodes of hypoglycemia (18.8% vs. 3.3%; p = 0.02), spontaneous severe hypoglycemia (12.5% vs. 0%; p = 0.006) and hyperglycemia (75.0% vs. 45.9%; p = 0.04) were higher and more frequent in nonsurvivors. Three of 5393 blood samples (0.05%) met severe insulin-induced hypoglycemia criteria, and 74.4% of samples met the recommended range of 4.4-8.3 mmol/l. Patients who died experienced more episodes of hyperglycemia, spontaneous hypoglycemia and greater variation in the daily glycemia level. Daily glycemia variation is more reliable than a mean glycemic level in evaluating glucose homeostasis in septic patients. Few episodes of severe insulin-induced hypoglycemia occurred while using the nurse-controlled insulin therapy protocol.

Pregnancy insulin, glucose, and BMI contribute to birth outcomes in nondiabetic mothers.

OBJECTIVE—We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes.RESEARCH DESIGN AND METHODS—Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months.RESULTS—In the retrospective study, within the nondiabetic range (2.1–7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean ± SEM) 2.1 ± 0.8% (P = 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 ± 0.8% (P < 0.0001) rise in emergency cesarean delivery, a 3.1 ± 0.7% (P < 0.0001) rise in elective cesarean delivery, and a 46 ± 8 g (P < 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight >90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per +1 mmol/l [95% CI 1.15–5.93]) and prepregnancy BMI (1.10 per +1 kg/m2 [1.04–1.18]). The mother's higher fasting glycemia (P = 0.004), lower insulin sensitivity (P = 0.01), and lower insulin secretion (P = 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P < 0.05).CONCLUSIONS—Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Variation in glycemia during liver resection in patients with intrathecal morphine for postoperative pain relief

Variation in glycemia during liver resection in patients with intrathecal morphine for postoperative pain relief

Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes mellitus

Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients. Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean+/-SD, 33+/-15 months). LMW-F levels were also measured once in 112 healthy control subjects. Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean+/-SD), 5.4+/-1.9 AU/ml and 4.5+/-1.8 AU/ml respectively vs. 3.8+/-2.1 AU/ml; p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4+/-1.9 vs. 4.5+/-1.8 AU/ml; p=0.02). Rises in LMW-F levels in individual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance). LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.

A high-glycemic meal pattern elicited increased subjective appetite sensations in overweight and obese women

We examined the effects of variations in postprandial glycemia and insulinemia on subjective satiety in overweight and obese women. We altered the ingestion rate of a glucose beverage to model the postprandial effects of high- and low-glycemic meals. Fourteen women were tested in a within-subjects’ design with two conditions: (1) Rapid, with a large glucose beverage consumed with breakfast and lunch and (2) Slow, with the same volume of glucose beverage consumed in eight portions (one with each meal, and the remaining seven at 20-min intervals after each meal). Meals were identical in the two conditions. Subjective appetitive sensations were measured with visual analog scales before and after meals, and hourly after each meal until 5 pm. Serum glucose and insulin were measured at similar time points. Subjects reported higher ratings of hunger and prospective consumption in the Rapid versus Slow condition at 4 h after breakfast and several hours after lunch. Serum glucose was more strongly correlated with the appetitive ratings in the Rapid than the Slow condition, and explained more of the variance (20–31%) than insulin (2–4%). The results of this study support the glucostatic theory linking dynamic changes in blood glucose with appetitive sensations.

Regulation of gene expression by glucose

In addition to its metabolic function, glucose modulates gene expression which is crucial in adapting cells to variations in glycaemia. We summarize recent advances in our understanding of regulation of gene expression by glucose. In-vivo and in-vitro experiments demonstrated that glucose regulates the transcription of genes encoding not only lipogenic and glycolytic enzymes but also proteins involved in global cell functions. The molecular mechanisms have begun to be elucidated, and the transcription factor carbohydrate responsive element-binding protein has emerged as a key actor, at least in liver. More recently, other candidates have been proposed, such as liver X receptors. In pathological situations, altered glycaemic control, as observed in diabetes mellitus, is associated with increased risk for microvascular and macrovascular complications. Recent findings suggest that changes in gene expression occurring in response to hyperglycaemia represent a novel component of glucotoxicity. Until recently, the direct transcriptional effects of glucose were underestimated, and insulin was considered to be the major regulator of gene expression in response to glycaemic variation. The recent discovery and characterization of transcription factors mediating the glucose response demonstrate that glucose, like fatty acids and other key nutrients, can directly control gene expression.

Implications and Treatment of Acute Hyperglycemia in the Setting of Acute Myocardial Infarction

A 52-year-old obese male without a prior history of diabetes mellitus (DM) presented with angina and an anterior ST-segment–elevation myocardial infarction (STEMI). Physical examination and chest x-ray were consistent with congestive heart failure. Admission glucose was 230 mg/dL. Coronary angiography revealed an occluded left anterior descending coronary artery, and stenting reestablished TIMI grade 2 flow in that artery within 90 minutes of symptom onset. Left ventricular ejection fraction was 35% with severe anterior hypokinesis. Peak creatine kinase was 600 IU. The next day, fasting glucose was 180 mg/dL. An echocardiogram performed 6 weeks after discharge revealed an ejection fraction of 35% without change in the anterior wall motion. Fasting glucose as an outpatient was 156 mg/dL. The scenario described above is commonly encountered and illustrates how hyperglycemia can affect the outcome of patients with STEMI. Hyperglycemia could have affected the following features of this case: (1) Congestive heart failure was present despite only modest myocardial injury by creatine kinase level; (2) despite successful percutaneous coronary intervention, subnormal coronary perfusion was observed; and (3) left ventricular recovery after STEMI did not occur. Cardiologists need to be cognizant of the hazards associated with hyperglycemia in this setting because these patients will be encountered more frequently as a result of the increasing prevalence of insulin resistance syndromes. Acute hyperglycemia is common in patients with STEMI even in the absence of a history of type 2 DM. Hyperglycemia is encountered in up to 50% of all STEMI patients, whereas previously diagnosed DM is present in only 20% to 25% of STEMI patients.1 The prevalence of type 2 DM or impaired glucose tolerance may be as high as 65% in MI patients without prior DM when oral glucose tolerance testing is performed.2 Elevated …

Relevance of Hyperglycemia on the Timing of Functional Loss of Allogeneic Islet Transplants: Implication for Mouse Model

The role of recipient hyperglycemia on timing of allograft survival is unknown. In this study, we investigated if and how variation in recipient glycemia affects the ability to achieve and maintain normoglycemia after transplant of C57BL/6 islets into diabetic BALB/c mice. 85 diabetic BALB/c mice with non-fasting glycaemia ranging between 275 and 600 mg/dL were transplanted with 400 C57BL/6 islets. The time of rejection inversely correlated with the pre-transplant blood glucose concentration (P=0.004). All the 13 mice with normoglycemia beyond 50 days had pretransplant glycemia <450 mg/dL and the presence of autologous beta cell function was demonstrated in 8 (>100 days function) by the persistence of normoglycemia after allograft removal. The presence of immunosuppression (rapamycin plus FK506 plus anti-IL-2Ra chain mAbs, n=31; rapamycin plus IL-10; n=29) removed the influence of pretransplant hyperglycemia but after treatment withdrawn the timing and the probability of graft loss correlate with the pretransplant hyperglycemia. Pretransplant glycemia was inversely correlated with HOMA-B and serum insulin showing that a significant residual beta cell mass was present in mice with glycemia <450 mg/dL. This study demonstrates that the timing of functional loss of islets allotransplantation depends on the degree of recipient hyperglycemia. This potential bias should be kept in count in experimental results and a threshold that excludes moderate diabetes should be used in defining recipient's eligibility.

Ambulatory cardiac rehabilitation with individualized care after elective coronary angioplasty: one year outcome

Aims Evaluation of one year outcome of an individualized program of ambulatory cardiac rehabilitation and interventions of secondary prevention after elective PTCA. Methods and results According to personalization of cardiac rehabilitation and restenosis evaluation, three degrees of intervention in 256 patients were performed. During one year follow-up, two patients died (sudden death). Within 6 months, 84 (32%) experienced angina and 53 (20.8%) between 6 and 12 months. In total, 60 patients required repeated coronary angiography of which 42 underwent rePTCA. At one year follow-up, total serum cholesterol diminished from 209±40 to 195±49 mg/dl (P = 0.0004) and LDL-cholesterol from 137±36 to 119±31 mg/dl ( P< 0.0001). HDL-cholesterol increased from 43±11 to 47±12 mg/dl ( P< 0.0001) whereas smokers diminished from 92 to 8 (36.2% vs 3.1%). Systolic blood pressure diminished from 140±22 to 135±12 mmHg ( P< 0.0001). Before PTCA, 53% of patients were physically very active and increased to 67% after one year (P = 0.008). Weight increased from 77.9 to 78.5 (P = 0.015). There were no significant variations in glycaemia (diabetic patients). After 6 months, 50 out of 64 working patients (78%) returned to work. Anxiety, depression and quality of life (SF-36) scores showed a greater improvement in males. The mean costs of three degrees of intervention were: (1) extensive: € 1085.50; (2) short: € 836.40; (3) without exercise training: € 246.90. Conclusions The present results indicate that, after PTCA, ambulatory cardiac rehabilitation with individualized care approach is safe and not expensive. After one year, the risk factor levels improved significantly except glycaemia in diabetics and weight.

Digestibilidade total, ileal e cecal e variação pós-prandial da glicemia em ratos alimentados com amido gelatinizado de mandioca.

&lt;span class="texto"&gt;A digestibilidade total, ileal e cecal, a porcentagem de digesta chegando ao íleo e o valor de suas correlações com a glicose sangüínea são importantes informações para a estimativa do valor nutricional do amido e do regime alimentar do qual ele participa. Com o objetivo de determinar a digestibilidade total, ileal e cecal de um alimento e de seu amido, a porcentagem de digesta chegando ao íleo e a correlação entre esta e as variações da glicemia pós-prandial em ratos, nos mesmos intervalos de tempo, realizou-se um trabalho piloto com dez ratos Wistar alimentados com dieta composta de uma base protéica adicionada de amido gelatinizado de mandioca. Os resultados de digestibilidade total, ileal e cecal e a porcentagem de digesta chegando ao íleo foram obtidos pela análise das fezes e do conteúdo ileal e cecal com auxílio do Cr2O3. Nos mesmos intervalos de tempo (0, 30, 60, 90 e 120 minutos pós-prandiais), o sangue foi coletado e a dosagem de glicose foi obtida através de kit enzimático. Os resultados indicam uma alta correlação entre a porcentagem de digesta chegando ao íleo e a glicemia, bem como um alto valor de digestibilidade do amido gelatinizado de mandioca, condizendo com resultados de outros estudos de digestibilidade realizados com amidos gelatinizados.&lt;/span&gt;

Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects

To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7-36)amide/(7-37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7-36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7-36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs. 50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C; similar results were obtained in a buffer solution containing DPP-IV. Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.

GLUT2 in pancreatic and extra-pancreatic gluco-detection (review).

Detection of variations in blood glucose concentrations by pancreatic beta-cells and a subsequent appropriate secretion of insulin are key events in the control of glucose homeostasis. Because a decreased capability to sense glycemic changes is a hallmark of type 2 diabetes, the glucose signalling pathway leading to insulin secretion in pancreatic beta-cells has been extensively studied. This signalling mechanism depends on glucose metabolism and requires the presence of specific molecules such as GLUT2, glucokinase and the K(ATP) channel subunits Kir6.2 and SUR1. Other cells are also able to sense variations in glycemia or in local glucose concentrations and to modulate different physiological functions participating in the general control of glucose and energy homeostasis. These include cells forming the hepatoportal vein glucose sensor, which controls glucose storage in the liver, counterregulation, food intake and glucose utilization by peripheral tissues and neurons in the hypothalamus and brainstem whose firing rates are modulated by local variations in glucose concentrations or, when not protected by a blood-brain barrier, directly by changes in blood glucose levels. These glucose-sensing neurons are involved in the control of insulin and glucagon secretion, food intake and energy expenditure. Here, recent physiological studies performed with GLUT2-/- mice will be described, which indicate that this transporter is essential for glucose sensing by pancreatic beta-cells, by the hepatoportal sensor and by sensors, probably located centrally, which control activity of the autonomic nervous system and stimulate glucagon secretion. These studies may pave the way to a fine dissection of the molecular and cellular components of extra-pancreatic glucose sensors involved in the control of glucose and energy homeostasis.

Relative contributions of β-cell function and tissue insulin sensitivity to fasting and postglucose-load glycemia

We performed hyperglycemic clamps in 283 nondiabetic Caucasians and, with multiple linear regression, determined the contribution of β-cell function and tissue insulin sensitivity to variations in glycemia and insulinemia during oral glucose tolerance tests (OGTTs). Impaired glucose tolerance (IGT) subjects had reduced insulin sensitivity ( P < .02) and β-cell function ( P < .0001). Normal glucose tolerance (NGT) subjects with first-degree type 2 diabetic relatives had reduced first and second phase insulin secretion (both, P < .05), but normal insulin sensitivity ( P = .37). β-Cell function and insulin sensitivity accounted for one fourth of the variability in glucose tolerance. Fasting plasma glucose in subjects with NGT (n = 185) was a function of both phases of insulin secretion and of insulin sensitivity (all, P < .05), whereas, in IGT subjects (n = 98), it was a function of first phase insulin secretion and insulin sensitivity ( P < .01). Two-hour glycemia was a function of second phase secretion and insulin sensitivity ( P < .01). Fasting and 2-hour plasma insulin levels were determined by insulin sensitivity (and glycemia) in NGT subjects ( P < .001), but by second phase secretion in IGT ( P < .001). We conclude that β-cell function is reduced in subjects with IGT; glycemia and insulinemia are not regulated by the same mechanisms in IGT and NGT; insulin sensitivity does not contribute to insulinemia in IGT; family history of diabetes influences β-cell function, but not insulin sensitivity in Caucasians.

Pancreatic α Cell Function in the Fetal Foal During Late Gestation

Plasma glucagon concentrations were measured in chronically catheterized fetal ponies and their mothers between 260 days of gestation and term (approximately 335 days). Fetal alpha cell responses to arginine and variations in fetal glycaemia were also examined during late gestation. Immunoreactive glucagon was present in fetal plasma at 260 days of gestation and its concentration in utero increased after 320 days and then again at birth. Maternal plasma glucagon concentrations were higher after 300 days than earlier in gestation but were lower than the corresponding fetal value throughout the period of gestation studied. Fetal alpha cells responded rapidly to intravenous arginine infusion but not to changes in the fetal glucose level induced by maternal fasting for 36 h or by intrafetal infusion of glucose. The maximal increment in fetal plasma glucagon in response to arginine occurred at the end of the 5 min infusion and was positively correlated to the basal pre-infusion plasma glucagon concentrations. Fetal plasma glucagon concentrations were unaffected by either hyper- or hypoglycaemia. In contrast, maternal plasma glucagon levels were significantly increased by fasting. These observations indicate that equine pancreatic alpha cells are functional in utero but that they are unresponsive to variations in glycaemia until after birth.

PANCREATIC [alpha] CELL FUNCTION IN THE FETAL FOAL DURING LATE GESTATION

Plasma glucagon concentrations were measured in chronically catheterized fetal ponies and their mothers between 260 days of gestation and term (~ 335 days). Fetal [alpha] cell responses to arginine and variations in fetal glycaemia were also examined during late gestation. Immunoreactive glucagon was present in fetal plasma at 260 days of gestation and its concentration in utero increased after 320 days and then again at birth. Maternal plasma glucagon concentrations were higher after 300 days than earlier in gestation but were lower than the corresponding fetal value throughout the period of gestation studied. Fetal [alpha] cells responded rapidly to intravenous arginine infusion but not to changes in the fetal glucose level induced by maternal fasting for 36 h or by intrafetal infusion of glucose. The maximal increment in fetal plasma glucagon in response to arginine occurred at the end of the 5 min infusion and was positively correlated to the basal pre-infusion plasma glucagon concentrations. Fetal plasma glucagon concentrations were unaffected by either hyper- or hypoglycaemia. In contrast, maternal plasma glucagon levels were significantly increased by fasting. These observations indicate that equine pancreatic [alpha] cells are functional in utero but that they are unresponsive to variations in glycaemia until after birth.

Melanin-concentrating hormone expression in slice cultures of rat hypothalamus is not affected by 2-deoxyglucose

In rats, melanin-concentrating hormone (MCH) neurons are mainly located within the lateral hypothalamic area (LHA). This area is known to be involved in the control of feeding and to contain glucose-sensitive cells. As a role for MCH in the regulation of food intake has been reported, we investigated the effects of 2-deoxyglucose (2DG) on MCH expression in cultured LHA slices, to verify if MCH neurons are sensitive to local glucoprivation through a modulation of MCH synthesis. After a 2–10 h 2DG incubation, competitive reverse transcription-polymerase chain reaction (RT-PCR) did not show any variation of MCH mRNA; no change was also observed in MCH immunocytochemical labeling. A slight decrease of MCH mRNA (5–15%) after a 17 h 2DG treatment might be due to a general degradation of neurons induced by long-term glucoprivation. In conclusion, we suggest that MCH neurons are not the glucose-sensitive cells previously described in the LHA and that the signals inducing their previously reported response to glycemia variations do not arise from the LHA itself.

Variation in the AU(AT)-rich element within the 3'-untranslated region of PPP1R3 is associated with variation in plasma glucose in aboriginal Canadians.

We are investigating associations between variations in candidate genes on chromosome 7q and diabetes-related phenotypes in Canadian Oji-Cree. One of these genes encodes the skeletal muscle regulatory G subunit of the glycogen-associated form of protein phosphatase 1 (PPPIR3), which may play a key role in muscle glycogen metabolism. There is a common 5-bp insertion-deletion polymorphism in a messenger ribonucleic acid-stabilizing AU(AT)-rich element within the 3'-untranslated region (UTR) of PPPIR3. The D allele had a frequency of 0.30 in the Oji-Cree. We found that this 3'-UTR variation of PPPIR3 was significantly associated with variation in 2-h postprandial glucose in adult Oji-Cree with type 2 diabetes or impaired glucose tolerance (IGT). Specifically, Oji-Cree with diabetes or IGT who were D/D homozygotes had significantly lower 2-h postprandial plasma glucose than subjects with the other genotypes. There was no association of the PPPIR3 genotype either with the presence of type 2 diabetes or IGT or with other quantitative traits in this sample. These findings suggest that common PPPIR3 3'-UTR variation that potentially affects messenger ribonucleic acid stability is associated with variation in glycemia in Oji-Cree subjects with type 2 diabetes.

A new Glucose Clamp Algorithm: Clinical Validation

A new glucose clamp technique for in vivo studies of insulin sensitivity was validated clinically. Eighteen patients (10 males, 8 females, age 35-80 years, body mass index 34.6-17.04) were connected to a computer-assisted artificial pancreas "Betalike R", using a new algorithm based on a "minimal model", to carry out the glucose clamp technique automatically and especially to overcome the well-known problems of its priming phase. We performed the euglycemic hyperinsulinemic clamp in four patients and the hyperglycemic hyperinsulinemic clamp in 14. In one patient both clamps were done. The mean priming time to reach steady-state glycemia was 20 min. Plasma insulin concentrations were measured every 20 min. This new automatic glucose clamp technique enables the priming phase to be run without any significant overshoot, and accidental variations of glycemia in steady state were reduced to a minimum. The system showed satisfactory safety and stability in controlling the patient's glycemia and assured high speed of the priming phase.

Effect of insulin on d-glucose transport by human placental brush border membranes

We studied the effect of insulin on the uptake of d-glucose by human placental brush border membranes (BBM) in vitro. d-glucose transport through placental BBM is a Na +-independent transport, inhibited by 0.5 mM phloretin. Increasing the substrate concentration from 1 to 50 mM resulted in an increase in glucose uptake according to an S-shaped relationship. Hill plot analysis suggests that at least two molecules of d-glucose are transported at the same time by the carrier. Preincubation of the placental tissue with insulin for 45 min at 22 °C significantly enhanced the d-glucose influx into the membrane vesicles, without influencing the slope of the Hill plot. A dose-response curve of the effect of insulin revealed that although the effect was already significant at 10 −9 M, the maximal activity was reached at 10 −8 M. The influence of insulin on d-glucose uptake was present only when preincubation of the placental tissue with the hormone was performed in the presence of Mn 2+. Incubation of placental tissue with 10 -8 M insulin did not influence d-glucose efflux from the BBM vesicles. Finally, direct incubation of the membranes with insulin had no effect on the glucose influx into these membrane vesicles. We conclude that insulin, at physiological concentrations, enhances glucose uptake by the BBM, and that such a regulation might contribute to the glucose homeostasis in the fetal circulation, independent of the maternal variations in glycemia.

The relationship of plasma acetate with glucose and other blood intermediary metabolites in non-diabetic and diabetic subjects

In investigating the interrelations of plasma acetate with glucose metabolism, we established that fasting plasma acetate levels (mmol/1) were greater in the diabetic than non-diabetic individuals ( p < 0.001). Plasma acetate and glucose levels correlated in all subjects (non-diabetic and diabetic) as a whole ( r s 0.28, p < 0.0001) and in the diabetics alone ( r s 0.35, p < 0.001). After i.v. glucose (20 g/m 2 body surface area), plasma acetate levels increased further in the diabetic and non-diabetic individuals. Plasma acetate also increased when non-diabetic individuals consumed 75 g oral glucose. Moreover, while plasma acetate levels had returned to fasting values by 90 min in the non-diabetic subjects after oral and i.v. glucose, levels remained elevated in the diabetics after i.v. glucose. The K rate constant of glucose elimination after i.v. glucose in the diabetics correlated negatively with acetate values at many time points. In the non-diabetics, changing acetate and glucose levels after oral glucose also correlated at multiple time points. These results suggest that the plasma acetate level is influenced by variations in glycaemia and provide further evidence for an impaired rate of acetate metabolism in diabetes.