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Optimizing blood glucose control in type 2 diabetes: an approach based on fasting blood glucose measurements.

A structured approach to the management of Type 2 diabetes, aiming to reduce fasting blood glucose levels to near-normal, can provide effective blood glucose control with minimal risk of hypoglycaemia and in a manner acceptable to most patients. When the fasting blood glucose value is maintained in the region 4-6 mmol l-1, protein glycosylation and plasma triglyceride values usually become near-normal and this may help to prevent the development of long-term diabetic complications. We propose a simple management strategy, based on 3-monthly fasting blood glucose determination, which uses not more than two therapeutic agents at any one time. If diet and maximal oral therapy fail to keep fasting blood glucose levels below 6 mmol l-1 then the addition of a basal insulin supplement, e.g. from a once daily injection of ultralente insulin, can restore near-normal fasting blood glucose levels without the need for full insulin replacement therapy. In older patients, where long-term prevention of diabetic complications is not such an immediate priority, less strict blood glucose control may be reasonable, aiming to keep the fasting blood glucose values below 10 mmol l-1 in order to prevent symptoms secondary to glycosuria. Patients can be seen at a monthly general practice morning diabetic mini-clinic or with the aid of a nurse visiting elderly patients at home.

Blood Glucose↗

Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies.

BACKGROUND: The incidence of adefovir dipivoxil (ADV) nephrotoxicity has been previously reported with the 60 and 120 mg daily dose in human immunodeficiency virus (HIV). We report a complete analysis on the renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B. METHODS: To investigate the efficacy, safety, and the tolerability of two dosing regimens of ADV (10 mg daily or 30 mg daily), two double-blind, placebo-controlled studies were performed in patients with chronic hepatitis B and compensated liver disease who were not undergoing current treatment and who had evidence of hepatitis B virus (HBV) replication. RESULTS: There was no overall median change from baseline at week 48 in serum creatinine or serum phosphorus levels in the ADV 10 mg group. In the ADV 30 mg group there was a slight increase of 0.2 mg/dL in median serum creatinine levels, and decrease of 0.1 mg/dL in serum phosphorus levels at week 48. Serum creatinine increase and hypophosphatemia were more frequently observed in patients receiving ADV 30 mg daily compared with ADV 10 mg and placebo. There were no grade 4 proteinuria, hematuria, or glycosuria events. CONCLUSION: Mild nephrotoxicity was demonstrated with the dose of 30 mg daily. Nephrotoxicity, as defined by an increase >/=0.5 mg/dL from baseline in serum creatinine or a serum phosphorus value of <1.5 mg/dL on two consecutive occasions, was not observed in patients treated with ADV 10 mg for a median follow-up period of approximately 64 weeks.

Adenine↗

Hemoglobin A1c (HbA1c) in children with long standing and newly diagnosed diabetes mellitus.

In 35 children with long-standing diabetes mellitus, a significant correlation was found between the hemoglobin A1c (HbA1c)--and the 24-hour urinary glucose excretion. By contrast, 11 newly diagnosed diabetic children had grossly elevated HbA1c-concentrations, but no correlations could be established between the levels of HbA1c and the duration of symptoms, blood glucose, glycosuria, ketonuria and the acid--base status. However, HbA1c and C-peptide were significantly correlated. The elevated HbA1c-concentrations decreased towards normal in all of these 11 children after 2--3 months following adequate therapy. The results suggest that the determination of HbA1c may serve as a valuable metabolic control index in children with long-standing diabetes mellitus, but adds little information in newly diagnosed patients. For the individual diabetic child during the early treatment period, HbA1c may be the index of choice for adequacy of metabolic control.

Acid-Base Equilibrium↗

Hyperpyruvaturia in experimental diabetes.

1. The 24 hourly excretion of pyruvate and glucose has been measured in alloxan-diabetic rats.2. The animals were allowed a 6-day control period before being injected with alloxan (I.V. 50 mg/kg body weight). The diabetes was treated by daily injections of insulin for a period of 6 days from the 7th to the 12th day following the alloxan injection.3. The pyruvate excretion increased more than 5-fold following the induction of diabetes, the values being 189 +/- 130 (S.D.) mug/24 hr in the control period rising to an average of 1002 +/- 664 (S.D.) mug/24 hr over the first 6 days of diabetes. The administration of insulin over the second 6-day period of diabetes caused the pyruvate excretion to decrease-though not significantly. Upon the withdrawal of the insulin treatment the pyruvate excretion increased significantly from 785 +/- 315 (S.D.) mug/24 hr to 2105 +/- 679 (S.D.) mug/24 hr, measured over a 5-day period. The final period of pyruvate excretion was significantly greater than the excretion over the first diabetic period.4. The glucose excretion during the initial diabetic period was 6.75 +/- 2.64 (S.D.) g/24 hr. The administration of insulin caused a 42% decrease in glucose excretion compared to a decrease of 22% for the pyruvate. The withdrawal of insulin caused the glucose excretion to increase by 149% while the pyruvate excretion increased by 157%.5. Diabetes was also induced temporarily by injections of anti-insulin serum and diazoxide. In each case significant glycosuria and hyperpyruvaturia were produced.6. The possible causes of the hyperpyruvaturia in diabetes are discussed.

Animals↗

Screening for inherited metabolic disease in Wales using urine-impregnated filter paper.

Urine specimens from 135 295 infants have been collected on filter papers and tested for 7 abnormal urinary constituents using spot tests and paper chromatography. The method has detected 5 infants with phenylketonuria, 4 with histidinaemia, 5 with cystinuria, 5 with diabetes mellitus, and one with alcaptonuria. Transient abnormalities such as tyrosyluria, generalized aminoaciduria, cystinuria, and glycosuria have been noted. 2 phenylketonuric infants failed to excrete a detectable quantity of o-hydroxyphenlacetic acid at the time of testing. The findings show that the detection of this compound in urine is an unreliable method of screening for phenylketonuria.

Alkaptonuria↗

Theophylline toxicity in a neonate.

One of a pair of preterm twins treated with theophylline (2 mg/kg per day) for apnoea developed episodes of hyperglycaemia in glycosuria.

Apnea↗

Arterial pressures in rural and urban populations in Nigeria.

Surveys of arterial pressure carried out in rural and urban communities in Western Nigeria showed a steady rise in systolic values with age, this trend being less marked with diastolic pressures. Blood pressure levels were similar in women from rural and urban areas, but seemed much higher in urban than in rural men. The incidence of proteinuria was lowest in the female urban group. In general, the incidence of proteinuria or glycosuria was low and did not appear to be related to the blood pressure.

Adolescent↗

Guar crispbread in the diabetic diet.

Nine diabetic patients who were receiving various treatments supplemented their normal home diets (two patients) or metabolic ward diets (seven patients) with guar crispbread for five days. Their mean urinary glucose excretion fell significantly by 38% during the last two days. A significant fall in fasting blood glucose concentration of 1.1 +/- 0.4 mmol/1 (19.8 +/- 7.2 mg/100 ml) was seen only in those who took guar after the control period. Over eight weeks' treatment insulin dosage was reduced by 21% in five patients, and home testing showed that glycosuria was reduced by 68% in six patients. Guar crispbread is likely to be a useful adjunct to diabetic treatment irrespective of the type of treatment or insulin dosage used.

Adult↗

Prevalence of symptomless urinary tract disease in Birmingham schoolchildren. I. Pyuria and bacteriuria.

In a pilot project 2,122 schoolchildren were screened for symptomless urinary tract disease by the examination of midstream urine specimens. These were tested for albumin, blood, and glucose with Labstix commercial strips, together with microscopy for abnormal cellular excretion.One case of renal glycosuria was found but none of previously undiagnosed diabetes mellitus. Out of 1,096 boys, 11 (1%) had pyuria-a leucocyte count greater than 10/cu.mm.-but only four showed abnormal counts on retesting. None had urinary tract infection.Out of 1,026 girls, 96 (9.3%) had pyuria initially but 35 were normal on retesting. Of the remaining 61 girls, 59 attended the outpatients department for further investigation, and in 30 vulvitis appeared to be the sole cause. Ten were proved to have significant bacteriuria and six of them showed radiological abnormalities.It is suggested that careful long-term studies are needed to study the economics and the implications of screening on a national scale.

Adolescent↗

Hypophosphataemic osteomalacia associated with a malignant tumour of the tibia: report of a case.

A case of vitamin D resistant hypophosphataemic osteomalacia with glycosuria and aminoaciduria is reported. The course of the disease was dramatically altered by the removal of a bone sarcoma which probably had been growing slowly since the onset of the patient's symptoms five years previously. The histology and electron microscopy of the tumour are described. Three years after the operation the patient remains free of symptoms.

Adult↗

Is questionnaire information valid in the study of a chronic disease such as diabetes? The Nord-Trøndelag diabetes study.

STUDY OBJECTIVE: The aim was to validate information about diabetes mellitus collected by questionnaire in a large epidemiological survey. DESIGN: Questions on diabetes diagnosis, medical treatment for diabetes, diabetes duration, and hypertension treatment were selected from the Nord-Trøndelag health survey questionnaires. One of the municipalities was selected for the validation study. SETTING: The health survey 1984-86 addressed all inhabitants > or = 20 years of age in Nord-Trøndelag county, Norway; 76,885 (90.3%) of the eligible population participated in answering the question on diabetes. PARTICIPANTS: All inhabitants in the municipality answering "yes" to the question on diabetes (n = 169) and the persons with the same sex born closest before and after each diabetic patient and answering "no" to the diabetes question (n = 338) were included. MEASUREMENTS AND MAIN RESULTS: A very thorough search was made in the medical files of the general practitioners in the municipality for corresponding information. Compared to the files, diabetes was verified in 163 out of the 169. The commonest cause of discrepancy was renal glycosuria. One out of the 338 registered non-diabetic persons was found to have diabetes. Diabetic patients tended to overestimate diabetes duration significantly. Insulin treatment was verified in 19/20 (95%) and treatment with oral hypoglycaemic agents in all 44 with an affirmative questionnaire answer. A negative answer on insulin and oral hypoglycaemic agents was verified in 100% and 99% respectively. CONCLUSIONS: The concordance was considerably higher than in a comparable Norwegian study performed 10 years earlier. Patient administered questionnaires may be a very reliable source of information for epidemiological purposes in a well defined chronic disease such as diabetes mellitus.

Adult↗

Observations on cardiovascular and neuroendocrine disturbance in the Guillain-Barré syndrome.

Cardiovascular disturbances were found to be a common feature of patients with the Guillian-Barré syndrome who were severely paralysed, requiring assisted ventilation. Glycosuria was noted in association with these disturbances, and in five patients investigated we found impaired glucose tolerance tests at the height of the paralysis. Catecholamine and 17-hydroxycorticosteroid urinary excretions were found to be high in four patients investigated when the neuropathy was most severe, and in one patient plasma cortisol levels were high with loss of diurnal variation. With recovery from paralysis cardiovascular disturbances became less marked, catecholamine and 17-hydroxycorticosteroid urinary excretions reverted to normal, glucose tolerance improved but remained abnormal in three patients during the period of observation. It is suggested that increased levels of catecholamines and cortisol contributed to the development of impaired glucose tolerance and cardiovascular disturbances.

17-Hydroxycorticosteroids↗

Epidermoid cyst of the pineal region.

An epidermoid cyst in the pineal region is reported to underscore the feasibility of successful surgical excision of such lesions and the need to review the management of posterior third ventricular lesions. An interesting, but unexplained, feature in this patient was renal glycosuria which cleared after excision of the tumour.

Brain Diseases↗

Glucose transporters.

The recent cloning of families of glucose transporters has made it possible to study their structure and their role in an increasing number of disease states. Two classes of glucose transporters transfer glucose across the plasma membrane of human cells. In epithelial cells lining the jejunum and proximal renal tubules, Na+/glucose cotransporters concentrate glucose inside cells using the transmembrane electrochemical potential of Na+. Molecular defects of different transporters of this class cause familial glucose-galactose malabsorption and renal glycosuria. In the basolateral membrane of epithelial cells and in nonepithelial cells, glucose flows down its concentration gradient through a family of facilitative glucose transporters. Reduced numbers of different facilitative glucose transporters may contribute to both defective insulin secretion and insulin resistance in diabetes mellitus and to neurological diseases associated with decreased cerebrospinal fluid glucose.

Blood Glucose↗

Alanine metabolism and gluconeogenesis in the rat.

The metabolism of alanine and several other gluconegoneic substrates was studied in anesthtized fed and fasted rats, i.e., rats with low and high rates of gluconeogenesis. Glutamine was released by the hindquarter (muscle) in both groups, whereas lactate, pyruvate, and alanine were taken up in fed rats and were released during starvation. Despite this, blood levels of alanine, lactate, and pyruvate were diminished in fasting rats, suggesting increased extraction by liver. Treatment of fasted rats for 24 h with phloridzin caused glycosuria and secondarily led to hypoglycemia and an intensification of the chargesobserved with fasting, i.e., hyperketonemia, hyperglucagonemia, and increased gluconeogenesis (assessed by urea N excretion). Blood alanine was decreased, even though the release of alanine from muscle was increased. Pretreatment with triamcinolone and administration of exogenous alanine both attenuated the hypoglycemia and ketosis, It is concluded that 1) in states of heightened gluconeogenesis, alanine release from muscle may not keep pace with extraction by liver and blood alanine decreases; 2) the release of alanine, lactate, and pyruvate from muscle parallel each other suggesting common control factors; and 3) in the red state muscle is an important site of lactate disposition.

Alanine↗

Changes in the growth hormone-IGF-I axis in non-obese diabetic mice.

We investigated the changes in GH-IGF-I axis in non-obese diabetic (NOD)-mice, a model of insulin-dependent diabetes mellitus. Diabetic female NOD mice and their age- and sex-matched controls were sacrificed at 4, 14, 21 and 30 days (30d DM) after the onset of glycosuria. Serum GH levels increased and serum IGF-I levels decreased in the 30d DM group (182 +/- 32% and 45 +/- 24% of age-matched controls respectively, p < 0.05). Another group (30d DM + I) was given SC insulin, and its serum IGF-I levels remained decreased. Liver GH receptor (GHR) and GH binding protein (GHBP) mRNA levels, as well as liver membrane GH binding assays were deeply decreased in the 30d DM group in comparison to controls. GHR message and binding capacity remained decreased in the 30d DM + I group. Renal GHR mRNA was decreased at 21d DM but not at 14d DM, whereas GHBP mRNA remained unchanged throughout the experiment. In conclusion, increased serum GH levels are documented in NOD diabetic mice, similarly to the changes described in humans. The decrease in GHR levels and decreased serum IGF-I in spite of increased circulating GH suggest a state of GH resistance.

Aging↗

Diminished proteinuria in diabetes mellitus by sorbinil, an aldose reductase inhibitor.

Proteinuria was diminished by concomitant oral administration of sorbinil, an aldose reductase inhibitor to streptozotocin-induced diabetic rats. Animals were placed in one of three groups: control, diabetic, sorbinil-treated diabetic. For a period of 10 weeks, 24-hour urine samples were analyzed weekly for volume, glucose, ketone, total protein (Pesce-Strande) and individual protein components having molecular weights between 15,000 and 120,000 daltons. The latter were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Results indicated that controls excreted albumin (68,000 daltons) and low-molecular weight proteins between 15,000 and 20,000 daltons. Throughout the 10-week period of diabetes, there was a 7- to 12-fold increase in total urinary protein excreted in 24 h. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins having molecular weights of 30,000-100,000 daltons and an increase amount of albumin. Sorbinil treatment prevented approximately 70% of the increase in total protein excretion despite persistent hyperglycemia, glycosuria and ketonuria. Laser densitometric analysis indicated that the aldose reductase inhibitor decreased by 70% the excretion of newly detected proteins and albumin while maintaining the 15,000- to 20,000-dalton proteins. These results suggest that the polyol pathway is implicated in diabetic-induced proteinuria and inhibition of aldose reductase may represent a therapeutic approach for management of diabetic nephropathy.

Aldehyde Reductase↗