Initial Blood Glucose Levels Research Articles

Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes—results of a hyperglycaemic glucose clamp study

The purpose of this study was to investigate renal glucose excretion as a function of blood glucose concentration and to evaluate the within-subject variability and between-subject variability in subjects with type 2 diabetes. Twenty-two subjects with type 2 diabetes [age 58 (12) years, diabetes duration 7 (6) years, endogenous creatinine clearance 117 (38) ml min(-1) 1.73 m(-2); median (inter-quartile range, IQR)] underwent two five-period hyperglycaemic glucose clamp experiments at intervals of 7-21 days. Starting from an initial blood glucose level of 12.2 mmol l(-1), subsequent glucose clamp levels were chosen using an algorithm based on urinary glucose concentrations measured at the end of the preceding glucose clamp period. That is, blood glucose was either stepwise decreased or increased depending on whether urinary glucose concentration was above or below 11.1 mmol l(-1), respectively. As expected, increasing the blood glucose from 7.8 to 13.3 mmol l(-1) during the glucose clamps resulted in a steep increase of urinary glucose excretion from 0.06 to 0.77 mmol min(-1). With decreasing blood glucose, a measurable glucosuria persisted up to a blood glucose level of 7.8 mmol l(-1). When defining the (pseudo)threshold for renal glucose excretion (PRT(G)) as the highest blood glucose level during glucose clamps associated with a concomitant glucose concentration in urine of <2.8 mmol l(-1), median (IQR) PRT(G) was 11.0 (1.1) mmol l(-1). The within-subject variability of PRT(G), i.e. the difference between two assessments, was low, 0.1 (0.0) mmol l(-1) while the between-subject variability of PRT(G) was high, ranging from 7.7 to 12.2 mmol l(-1). Renal glucose excretion increases in a proportional manner with increasing blood glucose. When decreasing blood glucose to euglycaemic blood glucose levels, glucosuria persists so that the classical concept of a renal threshold for glucose excretion cannot be upheld in subjects with type 2 diabetes.

Decreased Mortality by Normalizing Blood Glucose after Acute Ischemic Stroke

Hyperglycemia after cerebral ischemia exacerbates brain injury and worsens the outcome of stroke patients. The authors sought to examine the effect of glycemic control on mortality after acute stroke. This was a retrospective study of patients discharged with a diagnosis of ischemic stroke during a 40-month period from a large urban U.S. health system. Patients were compared by initial blood glucose (BG) levels and by glycemic control during the first 48 hours of hospitalization. Of 960 patients with thromboembolic stroke, 373 (38.9%) were hyperglycemic (BG > or = 130 mg/dL) on hospital admission. Admission hyperglycemia was associated with a higher mortality rate than was euglycemia (odds ratio [OR] = 3.15; 95% confidence interval [CI] = 1.45 to 6.85; p = 0.004). Persistent hyperglycemia (PerHyp) during 48 hours of hospitalization was associated with even higher mortality rate (unadjusted logistic regression, OR = 6.54; 95% CI = 2.41 to 17.87; p < 0.001). Glycemic control (normalization of BG to < 130 mg/dL) was associated with a 4.6-fold decrease in mortality risk as compared with the case of patients with PerHyp (p < 0.001). Multiple logistic regression showed glycemic control to be a strong independent determinant of survival (OR = 5.95; 95% CI = 1.24 to 28.6; p = 0.026) after acute stroke even after adjustment for age, gender, concomitant hypertension and diabetes, and stroke severity. Admission hyperglycemia is associated with a worse outcome after stroke than is euglycemia. Normalization of blood glucose during the first 48 hours of hospitalization appears to confer a potent survival benefit in patients with thromboembolic stroke.

Der herzkranke Diabetiker und zerebrovaskuläre Erkrankungen

Diabetes has significant implications for cardiac surgery. It is not only a major risk factor for coronary heart disease but also increases the risk for cerebrovascular complications during heart surgery. Surgical technique is pivotal for the outcome. "Off-pump" surgery carries a lower risk for stroke than conventional heart surgery. When a stroke happens, diabetes plays also a major role for the final outcome. Initial blood glucose levels during a stroke and final outcome are highly correlated. Consequently, patients with ischemic stroke after cardiac surgery should be treated according to the current criteria for stroke treatment. This includes strict monitoring of blood glucose level and avoidance of hypo- as well as hyperglycemia.

Acute Amitraz Poisoning in Adults: Clinical Features, Laboratory Findings, and Management

Background. Amitraz is a formamidine pesticide widely used in agriculture and veterinary medicine as an insecticide and acaricide. Reports on amitraz poisoning in humans are not as prevalent as those in animals. Of human intoxications in the medical literature, the majority of intoxications are in children. The number of adult intoxications with amitraz is limited. Methods. In this study, we discuss the clinical features, laboratory findings, and management of 23 adults with amitraz poisoning cared for in our center. Data were extracted from the charts retrospectively, and included age, gender, mode of poisoning, initial symptoms, time to appearance of initial symptoms, clinical and laboratory findings, management, and prognosis. Results. Fourteen of 23 patients were female (61%). Ages ranged from 16 and 78 years (mean 38.6 ± 19.8 years). Twenty-one patients ingested amitraz orally while one was exposed through skin contact and one probably through skin contact and/or inhalation. Seven patients ingested amitraz with intent to commit suicide and 11 patients accidentally. Vomiting, altered consciousness, and drowsiness were the predominant initial symptoms. Initially, hypotension was present in seven patients (30%), bradycardia in two (8.7%), myosis in six (26%), and mydriasis (without atropine administration) in three (13%). Time to appearance of the initial symptoms ranged from 5 to 120 minutes. Laboratory findings included an initial blood glucose level higher than 120 mg/dL in 62% of patients (mean 191 ± 70 mg/dL) and elevations in AST levels in four patients (81 ± 28 U/L) and ALT levels in three (60 ± 14 U/L). Ten patients had central nervous system depression, which resolved spontaneously. Five patients required mechanical ventilation for respiratory depression (mean duration of mechanical ventilatory support: 50 ± 16 hours). Six patients were thought to have been poisoned with an organophosphate and three with a carbamate pesticide due to confusing clinical picture; four of these nine patients received pralidoxim. Conclusions. In spite of a rapidly progressing and life-threatening clinical picture, amitraz intoxication in humans carries a low morbidity and mortality when appropriate supportive treatment is given. No antidote has been developed for use in more serious cases. To prevent accidental ingestions, prominent and clear warning labels should be placed on its containers.

Effects of wild ginseng ( Panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats

The aim of this study was to examine the possible antioxidant activities of wild Panax ginseng leaf extract intake in streptozotocin (STZ)-induced diabetic rats (WGLE). Initial blood glucose levels increased abruptly after streptozotocin injection. After 4 weeks of WGLE supplementation, blood glucose levels were lower in animals fed 40 mg/kg (266 mg/dL) and 200 mg/kg (239 mg/dL) than those in no-WGLE fed diabetic rats (464 mg/dL). The concentration of blood TBARS, which are considered the main products of glucose oxidation in blood, was also lowered by WGLE supplementation. These results indicate that WGLE supplementation is involved in suppressing a sudden increase in blood glucose levels and a consequent decrease in TBARS levels in diabetic rats. TBARS levels in the liver, kidney and spleen of WGLE-fed diabetic groups were also significantly lower than in the control diabetic group indicating that oral administration of WGLE effectively suppresses lipid peroxidation that occurs in the organs of diabetic rats. Antioxidant activities of WGLE supplementation further extend in suppressing activities of antioxidant related enzymes, such as glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), in organs of diabetic rats. These results confirm the effectiveness of WGLE supplementation in detoxifying free radicals that are produced excessively in diabetic-induced complications.

Screening and diagnosis of gestational diabetes

Gestational diabetes mellitus (GDM) is a risk factor for the mother and foetus. The risks increase proportionally to the maternal blood sugar concentration along a glycaemic continuum. However, there is ongoing controversy about the objectives of active screening and diabetic and obstetrical management for GDM. Various screening and diagnostic tests are used. None of them offers the combination of qualities to be expected from a test: simplicity of use, reproducibility, specificity and sensitivity, but each of them provides a basis on which recommendations can be established. The need to screen GDM as a risk factor in the whole population of pregnant women has led us to propose the use of simple, universally applied test, such as the "practical" test constituted by the assay of fasting and post-prandial blood glucose levels. In addition to screening, a classification which will take into account the results of subsequent as well as initial blood glucose levels could be preferable to evaluate the management and results.

Transdermal delivery of insulin from a novel biphasic lipid system in diabetic rats.

Noninvasive transdermal insulin delivery could provide diabetic patients with sustained physiological levels of basal insulin in a pain-free manner. We have developed a novel transdermal lipid-based system (Biphasix) suitable for macromolecule delivery across the skin. The objective of this study was to evaluate the pharmacological effects of the Biphasix-insulin delivery system in a diabetic rat model. Transdermal patches (one per animal) containing Biphasix-insulin formulation (10 mg of recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 48 h. Blood glucose was monitored every 2-4 h using a Lifescan glucose meter. Serum insulin levels were analysed by enzyme-linked immunosorbent assay. A decrease in blood glucose of 43.7 +/- 3.8% (mean +/- SEM, n = 25) was observed compared with initial blood glucose levels. The duration of the response was 51.5 +/- 3.7 h (mean +/- SEM, n = 25). Serum insulin after application of the transdermal Biphasix-insulin patch was 20.08 +/- 5.44 micro IU/mL (mean +/- SEM, n = 13) during the steady state, which was not statistically different from the insulin levels obtained 2 h after subcutaneous injection of 1 mg of recombinant human insulin solution. Insulin bioavailability from the transdermal Biphasix-insulin patches was 21.5 +/- 6.9% (mean +/- SEM, n = 13) based on serum insulin and 39.5 +/- 8.5% (mean +/- SEM, n = 25) based on the pharmacodynamic blood glucose-lowering effects. The Biphasix system successfully delivered insulin transdermally, as evidenced by a significant sustained decrease in blood glucose in diabetic rats, with a corresponding increase in serum insulin. These results support the feasibility of developing a transdermal insulin patch for human applications.

Transdermal delivery of regular insulin to chronic diabetic rats: effect of skin preparation and electrical enhancement

The efficacy of passive transdermal versus electrically-enhanced, or iontophoretic delivery of insulin was studied. The effect of skin pre-treatment on iontophoretic delivery of insulin was also investigated. Rectangular pulses of 0.25 mA/cm 2 current amplitude, 2 kHz frequency, and 50% duty cycle were used as anodal stimulation for electrically enhanced transdermal delivery of insulin. Twenty (20) BB/Wor chronic diabetic adult male rats were shaved 48 h prior to the study, and some experimental groups had hair stubble removed with a depilatory lotion. The iontophoretic drug-containing electrode was filled with 3 ml of porcine regular insulin (100 IU/ml) which had been adjusted to an acidic pH of 3.68 using 0.1 M HCl. The iontophoretic electrodes were then adhered to the abdomen of the alert rat. Results of the iontophoretic procedure were quantified by monitoring changes in blood glucose levels. When insulin was placed on the shaved skin, blood glucose levels fell in the chronic diabetic rat. In general, glucose levels fell more quickly and more profoundly using an iontophoretic enhancement of transdermal insulin delivery. However, some skin preparations facilitated movement of insulin more efficiently. The most profound effect of lowered blood glucose occurred when a depilatory lotion was used on the day of the study in conjunction with iontophoresis, where blood glucose levels fell by 61% after 1 h of iontophoretic treatment. Results indicate that insulin was delivered passively at therapeutic levels when the skin had been treated with the depilatory lotion on the same day as the study, as measured through a reduction in blood glucose levels of 29% after 1 h of passive delivery. When the depilatory lotion was used 24 h prior to iontophoresis, blood glucose remained near initial blood glucose levels. In the groups that did not have the depilatory lotion applied, blood glucose levels fell by 8% after 1 h of iontophoretic insulin delivery. The experimental evidence indicates a substantial increase in the penetration of insulin with the same-day application of a depilatory lotion in conjunction with iontophoretic enhancement.

Biochemical and morpho-cytochemical evidence for the intestinal absorption of insulin in control and diabetic rats. Comparison between the effectiveness of duodenal and colon mucosa

A combined biochemical and morpho-cytochemical investigation was carried out in order to assess insulin absorption by the duodenal and colon epithelium. Insulin was introduced in the lumen of the rat duodenum or colon in combination with sodium cholate and aprotinin. Blood analysis made at several time points has demonstrated a rapid increase in circulating levels of insulin followed by significant and consistent decreases in blood glucose. This indicates that biologically active insulin is absorbed by the intestinal mucosa and transferred to the circulation. Because of the initial high blood glucose levels, the lowering of the glycaemic values was more significant in diabetic animals. Also, levels of circulating insulin remained higher for longer time when the administration was performed in the colon. The integrity of the intestinal wall after insulin administration, evaluated morphologically, was retained. Application of protein A-gold immunocytochemistry has established the pathway for insulin absorption. In both duodenal and colon epithelial cells the labelling for insulin was detected in the endosomal compartment, in the Golgi apparatus and in association with the baso-lateral plasma membrane interdigitations. Some labelling was also present in the interstitial space and in capillary endothelial plasmalemmal vesicles. Insulin introduced in the lumen of the rat duodenum and colon appears thus to be rapidly internalized by the epithelial cells and transferred through a transcytotic pathway to the interstitial space from which it reaches the blood circulation. This exogenous insulin then induces significant decreases in plasma glucose levels which lasts for several hours. The results obtained support the possibility for the clinical development of an oral preparation of insulin.

Elevated Initial Blood Glucose Levels and Poor Outcome Following Severe Brain Injuries in Children

To determine whether elevations in blood glucose levels were related to neurologic outcomes following severe brain injuries in children, 54 patients 16 years of age or younger admitted to a regional trauma center with a Glasgow Coma Scale score of 8 or less over a 2-year period were retrospectively reviewed. The mean initial blood glucose level on hospital admission was significantly higher in the 16 patients with outcomes of death or vegetative state in comparison with that of the 38 patients with outcomes of good recovery, moderate disability,or severe disability (288 mg/100 mL vs. 194 mg/100 mL, t = -2.74, p = 0.01). Blood glucose levels correlated significantly with indicators of the severity of the brain injury, which were also related to outcome. In contrast, blood glucose levels did not correlate with indicators of the severity of the extracranial injuries, although the latter were significantly related to outcome. Logistic regression analysis resulted in a model for prediction of outcome which included the Glasgow Coma Scale score on admission and the initial blood glucose level. The odds ratio of a poor outcome in this model in patients with blood glucose levels greater than or equal to 250 mg/100 mL relative to those with lower levels was 8.3 (95% confidence interval 1.3-53.6). A simple prognostic score was derived from the logistic regression which improved upon the prediction of outcome using the Glasgow Coma Scale score alone in those patients with initial blood glucose levels greater than or equal to 250 mg/100 mL.(ABSTRACT TRUNCATED AT 250 WORDS)

A Case of Diabetic Non-Ketotic Hyperosmolar Coma with an Increase with Plasma 3-Hydroxybutyrate.

We have seen a case of "diabetic non-ketotic hyperosmolar coma" with ketosis. An 84-year-old man was brought into the hospital in a deeply comatous and dehydrated state. The initial blood glucose level was 1252 mg/dl with plasma osmolarity of 435 mOsm/l, but no ketonuria was detected by the nitroprusside method (Ketostix). However, the plasma 3-hydroxybutyrate (3-OHBA) level was 5 mM in a newly developed bedside film test. The serum ketone bodies were later found to be 5.56 and 0.82 mmol/l for 3-OHBA and acetoacetate (AcAc), respectively. A marked increase in glucagon, cortisol and ADH with renal dysfunction (creatinine 5.0 mg/dl) were noted. An abnormal electrocardiogram, occular convergence and chorea like movement disappeared after correction of metabolic disturbances. The moderate level of IRI (14 microU/ml) on admission and a good response to glucagon 2 months after admission also indicate that the present case is a typical hyperosmolar non-ketotic coma. Because of a preferential increase in 3-OHBA, ketonuria seemed to be absent in the regular nitroprusside test. Marked dehydration is thought to cause renal dysfunction, and the increase in ADH may have helped to prevent further aggravation of ketoacidosis. We propose to change the term hyperosmolar non-ketotic coma (HNC) to diabetic hyperosmolar coma (DHC), because sometimes patients with hyperosmolar non-ketotic diabetic coma are ketotic, as seen in the present case. Determination of 3-OHBA or individual ketone bodies in blood is important and essential for the differential diagnosis of diabetic coma. The diagnosis of either ketoacidotic or hyperosmolar coma should be made depending on the major expression of ketoacidosis or hyperglycemic hyperosmolarity.

Deaths associated with diabetic ketoacidosis and hyperosmolar coma, 1973–1988 (for editorial comment, see page 427; see also page 444)

We assessed the possibility of improvements in the management of the potentially fatal acute hyperglycaemic complications of diabetes by a review of all deaths in patients who presented to the Alfred Hospital, Melbourne, with diabetic ketoacidosis or hyperosmolar coma during the 16 years, 1973-1988. All late deaths of patients during hospitalization were included in the mortality data. In the 610 episodes of diabetic ketoacidosis (pH, 7.30 or lower) or hyperosmolar coma (osmolality, 350 mOsmol/kg or greater), only one death occurred as a result of the acute metabolic disturbance--in a patient who had suffered a cardiac arrest before admission to hospital. The over-all mortality rate was 6.2% (38 deaths). The mortality rate was 4.9% (26 deaths) for 528 episodes of diabetic ketoacidosis and 14.6% (12 deaths) for 82 episodes of hyperosmolar coma. Patients with diabetic ketoacidosis who died were older than were those who survived (64 +/- 13 years compared with 40 +/- 21 years, respectively; P less than 0.001). Mortality in patients with hyperosmolar coma did not relate to age, initial blood-glucose level or osmolality. Twelve deaths resulted from bacterial pneumonia and two deaths resulted from aspiration pneumonia. Other major causes of death were mesenteric and iliac thromboses (six cases), myocardial infarction (eight cases) and cerebral haemorrhage (two cases). Of the 26 deaths that were associated with diabetic ketoacidosis, only two deaths--as a result of aspiration pneumonia and bowel infarction, respectively--were assessed as potentially avoidable after the patient's admission to hospital. Eight of the 12 hyperosmolar-coma-associated deaths occurred in newly recognized diabetic patients in whom there were avoidable delays in diagnosis. We conclude that further improvements in outcome will be difficult to achieve, but that efforts should be directed towards the earlier diagnosis of diabetes and the earlier recognition and treatment of associated acute pulmonary and vascular complications.

Risk factors for diabetic retinopathy: a population-based study in Rochester, Minnesota.

Retinopathy is an important sequela of diabetes mellitus, but clinical risk factors for this condition have rarely been assessed in a geographically defined population. In this population-based study, the 1135 Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort) were followed through their complete medical records in the community to January 1, 1982. Because most of the cases of diabetic retinopathy in Rochester residents developed in patients with non-insulin-dependent diabetes mellitus (NIDDM), risk factors for diabetic retinopathy were examined in this group (N = 1031). A proportional hazards model identified the following risk factors for diabetic retinopathy in NIDDM: elevated initial fasting blood glucose level, marked obesity, and earlier age at onset of diabetes. Stratified analyses indicated that duration of diabetes was also significantly associated with an increased risk of retinopathy. Two secular trends, increasing detection of "mild" NIDDM and decreasing risk of diabetic retinopathy, had a major effect on retinopathy risk assessment. These data also suggest that insulin therapy is not an independent risk factor for diabetic retinopathy.

Metabolic control and serum hormone levels in relation to retinopathy in diabetic pregnancy

The occurrence and progression of retinopathy were related to the mean blood glucose levels and the serum concentrations of prolactin, human placental lactogen, oestradiol and progesterone in 57 pregnant insulin-dependent diabetic patients. Fifteen patients had frank retinopathy, of whom eight showed a marked increase in retinopathy. The initial blood glucose levels were significantly higher in patients whose retinopathy progressed, whereas during the second and third trimester similar blood glucose levels were achieved in all groups. Serum concentrations of progesterone and human placental lactogen were significantly increased in diabetic patients during the last trimester when compared with those in normal pregnancies, and during the second trimester, patients with retinopathy showed significantly higher concentrations than those without, but no significant difference was found in oestradiol values. The eight patients with progressive retinopathy showed progesterone, human placental lactogen and oestradiol levels at or above the upper limit of the normal range. Throughout gestation, serum prolactin concentrations were significantly lower in diabetic patients than in healthy subjects. No correlation was found between serum prolactin values and the occurrence of retinopathy.

Effect of euglycemia on the outcome of pregnancy in insulin-dependent diabetic women as compared with normal control subjects

A comparative study was performed to evaluate the effect of a euglycemia program instituted prior to the 12th week of pregnancy in 52 diabetic women (White class B or greater). The comparison group consisted of 52 nondiabetic women of the same ethnic background, chosen serially over the period of study, who presented to the same clinic and delivered in the same fashion. Euglycemia in the diabetic group was documented by daily home-monitored glucose determinations and bimonthly hemoglobin A 1c levels, and 24-hour glucose profiles and urinary collections during periods of hospitalization, at presentation, 20 or 26 weeks, and at term. All but two women with diabetes agreed to follow the program. There was no fetal loss in the diabetic group, and mean percentile body weight was slightly less (58 percent compared with 62 percent, p = NS) than that of the offspring of the nondiabetic clinic comparison group. Infants of diabetic mothers who had vascular disease (White classes D 4, R and F) were smaller than infants of mothers from White classes B, C 1, BG and CG (p < 0.001). There was one blood glucose level of less than 45 mg/dl in one infant of a diabetic mother. None had a bilirubin level of more than 12 mg/dl versus the five in the control group (p = 0.03). No infant in the diabetic group had erythremia (hematocrit of more than 65 percent) or respiratory distress versus four with (p = 0.06) and five with (p = 0.03), respectively, in the clinic population. Only one infant in the comparison group and none in the diabetic group showed evidence of hypocalcemia (p = NS). The present study indicates that problems of morbidity and mortality are minimized if patients with diabetes are maintained euglycemic from the 12th gestational week on. The results of this comparative study was consistent with the hypothesis that if hyperglycemia is eliminated as a variable in diabetic pregnancy, outcome is determined by the quality of antenatal care rather than the presence of diabetes mellitus per se, even though patients in White classes D 4, R and F may deliver slightly smaller infants than diabetic mothers without concomitant vascular disease. Mothers in White classes D, R and F were found to have higher initial mean blood glucose levels and hemoglobin A 1c levels than the other diabetic women. Whether earlier establishment of euglycemia will eliminate the problems of growth retardation, fetal wastage and congenital malformation remains to be determined.

EFFECT OF DISCONTINUATION OF BIGUANIDE THERAPY ON METABOLIC CONTROL IN MATURITY-ONSET DIABETICS

Control of blood-glucose levels was monitored for 12 wk after withdrawal of biguanides in a group of 118 diabetic patients treated with biguanides (alone or in combination with sulphonylurea) from a population of 39 200. The mean fasting blood-glucose level rose during the first 2 wk from 9·2±0·3 to 11·3±0·4 mmol/l (p<0·001) and the mean urinary-glucose excretion from 11·7±3·7 g/24 h to 36·5±5.5 g/24 h (p<0·001), respectively. The change in blood-glucose concentration did not depend on age, sex, bodyweight, or duration of diabetes or biguanide treatment. The mean increase in blood-glucose was similar (2·1-3·1 mmol/l) in subjects with their initial blood-glucose level ≤6·0 mmol/l, 6·1-11·0 mmol/l, and ≥11·1 mmol/l. There were no changes in blood-lipids or bodyweight during the observation period. Biguanides reduced blood-glucose levels in most patients with maturity-onset diabetes. The hypoglycæmic effect was similar in subjects with normal and increased bodyweight and did not depend on the duration or severity of diabetes.

Severe hyperglycemia: effects of rehydration on endocrine derangements and blood glucose concentration.

Diabetic ketoacidosis is associated with an excess secretion of counterregulatory hormones. The effect of rehydration on these endocrine derangements before insulin administration is unknown. Therefore, we measured the effect of rehydration with hypoosmolal fluid (220 mosmol/kg) on blood glucose (BG), immunoreactive insulin (IRI), immunoreactive C-peptide (IRCP), immunoreactive glucagon (IRG), human pancreatic polypeptide (hPP), growth hormone (GH), prolactin (PRL), cortisol, aldosterone, renin (PRC), epinephrine, norepinepnrine, and parathyroid hormone (PTH) in ketoacidotic diabetic patients [pH 7.03 ± 0.05 (SEM); n = 8] and in patients (n = 2) with nonketotic hyperglycemia (BG, 29.8 mmol/L and 46.8 mmol/L). The cumulative net fluid balance after rehydration was 4364 ± 690 ml. Basal insulin was inappropriately low, and IRCP was below the normal range (1.5 ± 0.5 ng/ml). Serum osmolality fell during hypoosmolal rehydration (n = 9) from 335 ± 11 to 315 ± 9 mosmol/kg. Rehydration with hypoosmolal fluid with bicarbonate added at a pH of less than 7.2 induced a fall in BG ranging from 6.1 mmol/L to 22.6 mmol/L, or of 16.7% to 79.8% of the initial BG level, as well as a decrease in plasma lactate and urinary glucose. These effects were paralleled by a decrease in IRG, cortisol, epinephrine, norepinephrine, aldosterone, and PRC. No fall in BG was seen in one patient whose dehydrated state was maintained by infusion of isotonic saline. Low dose insulin treatment was initiated in all patients immediately when no further fall in blood glucose levels was achieved. We conclude that rehydration improves the metabolic situation in severe diabetic hyperglycemia and ketoacidosis by reducing (a) the availability of counterregulatory hormones and (b) peripheral insulin resistance on a cellular level. Thus, proper rehydration will support the beneficial action of simultaneous low dose insulin treatment in patients with severe hyperglycemia.

Studies of glycemia and glucosuria in diabetics after breakfast meals of different composition

In series I, The effect of four isocaloric, ordinary diabetic breakfast meals on the blood glucose level and on the urinary glucose loss was tested in 9 adult diabetes and three healthy subjects (ages 60 to 75) as well as in five insulin-treated diabetics (ages 18 to 40). All breakfasts derived 20% of the energy from protein, 35% from fat, and 45% from carbohydrates (CHO). The oligosaccharides amounted to 5, 30, 45, and 65% of CHO, respectively. In series II, four isocaloric breakfast meals with CHO amounting to 35 or 70% of the energy, oligosaccharides furnishing one-third or two-thirds of the CHO at each level, were tested in the same way in eight of adult diabetics and in the three healthy subjects. The two breakfasts with the highest percentage of oligosaccharides in series I caused the smallest increase in the blood glucose level in the adult subjects. In the adults as well as in the juveniles, these breakfasts gave rise to clear symptoms of hypoglycemia and/or a feeling of a deficient satiety in several subjects. In juveniles, the initial blood glucose level turned out to be of greater importance for the outcome of the test than the kind of carbohydrates consumed. In series II, The CHO-rich meals caused significantly greater blood glucose increases than did the low-CHO meals. Despite the unexpected findings that ordinary diabetics breakfast meals, high in oligosaccharides, gave a smaller increase in blood glucose than did meals in which wheat starch predominated, the use of diets rich in oligosaccharides should be avoided because of the risk of overconsumption owing to hypoglycemic symptoms or to the deficient feeling of satiety.

Abdominal Pain in Diabetic Metabolic Decompensation

Severe abdominal pain and tenderness occured in 46 of 211 episodes of severe diabetic metabolic decompensation. No association was found between abdominal pain and the degree of dehydration or the initial blood glucose level. In 17 instances, the abdominal pain could be attributed to the precipitating cause of the metabolic decompensation. The episodes of unexplained pain all occurred insulin-dependent patients less than 40 years of age; of these, only three had a plasma bicarbonate level greater than 10 mEq/liter, and in two patients, additional factors could account for the relative lack of ketoacidosis. Abdominal pain occurring in patients more than 40 years old, irrespective of the plasma bicarbonate level, and in patients of any age with a plasma bicarbonate level in excess of 10 mEq/liter, almost invariably indicates a specific underlying cause.

Photically-induced epilepsy and glucose metabolism in the adolescent baboon ( Papio papio)

Summary In 12 adolescent baboons (Papio papio) from Senegal an EEG study has been made of paroxysmal responses to intermittent light stimulation (ILS) in relation to blood glucose levels, and of the spontaneous paroxysmal activity occurring in insulin-induced hypoglycaemia. The severity of myoclonic or seizure responses to ILS did not correlate with initial blood glucose levels in the range 100–250 mg/100 ml. Bilateral tonic-clonic seizures induced by ILS were followed by a marked rise in blood glucose, maximal 20–40 min later. Prolonged myoclonia during ILS was not associated with such a hyperglycaemic response. Intermediate forms of seizure response were associated with intermediate degrees of hyperglycaemia. During insulin-induced hypoglycaemia myoclonic responses to ILS diminished. Large doses of insulin (300–540 I.U.) produced cortical slow waves, spikes and spikes and waves after 2–5 h. When the blood glucose had been below 25 mg/100 ml for more than 90 min clonic-tonic-clonic seizures occurred. The tonic phase of these seizures, unlike the tonic phase induced by ILS, was not accompanied by cortical high-voltage fast activity. The biochemical disorder promoting seizures in hypoglycaemia is concluded to be different from the abnormality underlying photically-induced seizures.