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Aims: Diabetes mellitus is a progressive, chronic, systemic, metabolic disease that must be managed effectively. Its prevalence is increasing rapidly. We investigated whether urologists’ awareness and recognition of glucosuria contributed to the diagnosis of diabetes and regulation of blood glucose. Methods: A total of 39,053 patients were retrospectively evaluated between January 2018 and February 2019. Of them, 16,211 had undergone urinalysis for varied reasons. Glucosuria was semi-quantitatively measured as (+), (++), (+++), and (++++). Patients were assessed in terms of whether they had been referred to endocrinology or internal medicine departments within the 15 days and the presence/absence of a previous or new diagnosis of diabetes mellitus by measuring blood glucose and HgbA1c levels. Results: Glucosuria was detected in 665 patients (4.1%), of whom 495 were included in the study. 417 (84.2%) had been previously diagnosed with diabetes mellitus, and 56 (11.3%) newly received a diabetes mellitus diagnosis. Blood glucose and HbA1c values were normal in 22 (4.4%) patients with glucosuria. HgbA1c value was determined as 7 or above in 381 (91.3%) of 417 cases with a previous diabetes mellitus diagnosis. Conclusion: Referring all patients detected to have glucosuria in the spot urine test at any time regardless of fasting/non-fasting to the relevant departments can contribute to the diagnosis and treatment of diabetes mellitus disease.

During preanesthesia evaluation, patient medications are reviewed and many are not administered on the day of surgery. Additionally, neurosurgical patients can develop postoperative encephalopathy from a variety of etiologies, including metabolic derangements. We report a case of postoperative neurosurgical euglycemic ketoacidosis which presented as unexplained encephalopathy and was the result of continued action of the patient’s serum glucose cotransporter-2 (SGLT-2) inhibitor combined with perioperative fasting. A 68-year-old woman with a history of type 2 diabetes mellitus was admitted to the neurocritical care service after resection of a left temporal meningioma. On postop day 1, she became lethargic and with worsening aphasia. Laboratory studies revealed blood glucose 140 to 160 mmol/L, bicarbonate 9 mmol/L, anion gap of 21, and pH of 7.2. Urine was positive for ketones and glucose, and serum was positive for β-hydroxybutyrate. Endocrinology was consulted and the patient was diagnosed with euglycemic diabetic ketoacidosis and treated with insulin until her anion gap closed. Over the next 2 days, her neurological examination improved to baseline. Although the patient did not take empagliflozin the day of surgery, the drug has a half-life of >12 hours, and other reports have described continued glycosuria for up to 10 days after drug discontinuation. This case illustrates the need for increased awareness of SGLT-2 inhibitors and “sweet pee encephalopathy” among neurosurgical and neurointensivist teams as well as potential modification of perioperative management of patients using newly emerging SGLT-2 inhibiting pharmaceuticals.

The aim of this study was to investigate the immunomodulatory capacity of native and Fe(II)-exposed intravenous immune globulin (IVIg) in multiple low dose streptozotocin-induced diabetes and to delineate the mechanisms of their influence on immune cell functions. Optimal doses (200–600mg/kg) of IVIg prevented the development of hyperglycemia, glycosuria and attenuated mononuclear cell infiltration in pancreatic islets. Fe(II) exposure of IVIg decreased their optimal therapeutic dose to 100mg/kg which significantly decreased the serum levels of proinflammatory cytokines compared to the same dose of native IVIg. This was accompanied by lower numbers of TNF-α, IFN-γ and IL-17 producing CD4+ T cells and increased frequencies of CD4+IL-10+ and CD4+IL-4+ T cells in the pancreatic lymph nodes and islets on day 16 after diabetes induction. Ferrous ion-exposed IVIg enhanced the bias towards Th2 response while the regulatory Foxp3+ T cells were not affected.

Dietary modification is considered a cornerstone in the management of diabetes superimposed upon which are pharmacological therapies as required. The value of hypocaloric diets in reducing and eliminating glycosuria was extolled in the pre-insulin era. A common feature of the nutrient balance of these diets was restriction in the availability of carbohydrate. Herein we review the use of diet as therapy in the past and discuss the rationale for hypocaloric dietary management of type 2 diabetes in the 21st century, drawing comparisons with bariatric surgery and considering why weight loss is particularly difficult for overweight and obese individuals with type 2 diabetes.

To recognize the clinical characteristics and outcomes of neonatal diabetes mellitus (NDM), the authors retrospectively reviewed 1 NDM baby in their department and compared their data with 39 NDM cases reported in the available Chinese literature between January 1986 and December 2010. Most of the cases were located near the eastern and southern coasts of China, and clinical manifestation of 72.5% of the cases occurred in 4-week-old infants. Hyperglycemia and glycosuria findings were seen in all the patients and in 47.5% with intrauterine growth retardation. Moreover, 30.0% of the cases had polyuria, 52.5% had dehydration, and 47.5% had ketoacidosis. Cases with hyperglycemia, dehydration, and ketoacidosis recovered mostly. Ten NDM cases had persisted after 1 to 11 years of follow-up, 3 cases maintained normal blood sugar, and 7 cases had poor sugar control. NDM is a rare condition and early management includes fluid and insulin and later management depends on the transient or permanent nature of the condition.

Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but might also lead to SCC in human oral mucosa. Thus, the present study was conducted to examine the effects of the antifungal agent itraconazole (ITCZ) on proliferative and inflammatory changes of the forestomach in alloxan-induced diabetic WBN/Kob rats. Diabetes was induced by alloxan at fifteen weeks of age. Rats were allocated to three groups at forty-five weeks of age and were given ITCZ by gavage 0 (vehicle control), 5, and 10 mg/kg/day for four weeks, and they were sacrificed at the sixty-fifth week of age. Mucosal hyperplastic changes were consistently accompanied by inflammation and Candida infections in the 0 mg/kg group. These lesions were reduced by ITCZ (0 mg/kg; 100%, 5 mg/kg; 53.5%, 10 mg/kg; 61.5%). Squamous cell carcinoma was detected in three rats from the 0 mg/kg, but only one rat from the 10 mg/kg dose groups in this study. Itraconazole reduced the degree of mucosal hyperplasia, inflammatory changes, and Candida infection. Therefore, C. albicans infection was an important factor in pathogenesis of mucosal proliferation and inflammation.

Systemic lupus erythematosus (SLE) often coexists with other diseases. Diabetes mellitus (DM) is an example and patients with overlap SLE-DM can present with clinical features common to both disorders. In this review, we describe the patients with overlap SLE-DM, focussing on the clinical features common to both diseases that these patients can present, and on the challenges of managing such complications. A detailed review of the patients’ notes ( n = 485) was performed. At every outpatient appointment the patients’ urine was tested for glucose, protein and blood. Patients with persistent glycosuria were investigated with fasting blood glucose and a glucose tolerance test to help make the diagnosis of DM. Particular note was made of those patients whose symptoms could be due to SLE, DM or both. Nine patients with DM were identified. Three had type 1 DM, four had type 2 DM and two were considered to have steroid-induced DM. Among these patients, three had renal involvement (two with WHO class IV lupus nephritis); two had peripheral neuropathy (one had a mixed sensory and motor neuropathy, one had a sensory peripheral neuropathy); two patients had retinopathy and cataracts and one had angina. The combination of SLE and DM is uncommon but the predisposition to renal, peripheral neuropathy and retinal disease means that great care must be taken when deciding which clinical feature is due to which disease, because active SLE requires additional immunosuppression whereas DM requires optimization of the metabolic control. Interestingly, although in theory patients with SLE and DM are in double-jeopardy of developing atherosclerosis, to date, only one of our overlap patients has developed angina.

Purpose Insulin therapy has been shown to benefit the prognosis in patients with type 2 diabetes, but its initiation and intensification is often delayed through concerns about hypoglycemia and weight gain. In addition, weight gain is linked to the pathophysiology of type 2 diabetes and contributes to the overall risk for adverse cardiovascular outcomes. This article attempts to summarize this issue and examine the options available for weight management. Methods A broad range of literature has been reviewed to distil important, consistent facts about insulin and weight gain and the options available for limiting the problem. Results Unfortunately, the great benefits of insulin therapy may be potentially undermined by weight gain. Weight gain is physiologically and psychologically undesirable, especially in patients with diabetes who are already overweight. The fear of weight gain with some medications contributes to psychological insulin resistance, which may discourage patients from commencing or following insulin regimens. However, new diabetes treatments and lifestyle interventions can be used to mitigate these problems. Conclusions The exact choice of insulin and oral medications and weight loss interventions are important considerations in the overall management of patients with type 2 diabetes. Changes in a patient’s lifestyle, such as modifications to diet and implementing an exercise program, are first-line treatments for type 2 diabetes and can also counteract insulin-induced weight gain.

A high-sucrose diet decreases dentin formation and its minerals, but the mechanisms behind the effect are largely unknown. We studied the combined and separate effects of sucrose and insulin on dentin formation and mineral metabolism in growing rats. At weaning, animals were randomized into 4 groups: control/sucrose diets both with and without external insulin (1 U/x 100 g body weight daily). After 4 weeks, we measured areas of dentin formation, numbers and areas of dentinal caries lesions, and serum and urine glucose, insulin, Ca, Na, K, and P. Exogenous insulin increased serum and urine insulin levels and decreased serum glucose level, but did not affect dentin formation or dentinal caries lesion formation or progression. A high-sucrose diet decreased dentin formation independently of insulin. The differences in serum and urine minerals between the groups were minor. The findings confirm that sucrose-diet-induced reduction in dentinogenesis is independent of insulin and loss of minerals in urine.

Progressive renal dysfunction in 5/6 nephrectomized (NX) rats can be physiologically divided into three stages, coinciding with morphological stages, after definition of physiological parameters for identification of stage. Now, for the establishment of a toxicity screening approach using 5/6 NX rats, our concept, “Differential toxicity synchronized with renal dysfunction process could be identified using 5/6 NX rats” was examined by dosing gentamicin. Firstly, electrophoretic fractional changes of urinary proteins during gentamicin treatment were clarified with determination of amino acid sequences and the three differential features were proven, revealing the unpredictable depression of urinary albumin with progression of the stages in NX rats. Secondly, marked elevation of urinary lactate dehydrogenase (LDH) and glucose (GLU) was evident, indicating the intensified hypoxic conditions and glycolysis in tubular cells synchronized with increased tubular damage. Thirdly, these transit metabolic changes were proven as intensive cause for the advancement of renal dysfunction by the reduction of FRelectrolytes and water at the end of each dosing period. These results indicate that toxicity studies of newly developed drugs using 5/6 NX rats have potentiality prior to clinical dosing to the patients.

Purpose A systemic disease may be diagnosed for the first time in patients who present to the eye department with ophthalmological manifestations. This study documents the pattern of systemic disorders which were encountered in an emergency eye clinic for the first time. Subjects and method. Over a period of six months details of all patients who had a previously unknown systemic condition diagnosed in the Emergency Eye Clinic were recorded. Patients were seen in this clinic upon referral from other practitioners. All patients, with the exception of those with minor ophthalmic problems, were screened for hypertension and glycosuria. The patients were subsequently referred to their general practitioner or the appropriate hospital specialist for further management. Results During this period 1025 new patients visited the emergency eye clinic. Previously undiagnosed systemic disease was present in 86 patients (8.4%). The commonest disorders were neurological 35 (41%), cardiovascular 17 (20%), glycosuria 13 (15%) and respiratory 5 (6%). Visual disturbance and pain were the most frequent ocular presentation. In 54 patients (62.8%) the ocular condition was a direct manifestation of the systemic condition and in 32 patients (37.2%) the systemic disease was a coincidental finding. Conclusions Awareness of ophthalmological manifestations of systemic disorders helps in the early diagnosis of these conditions and reduces the resulting morbidity and possibly mortality. This study illustrates the hidden role of the emergency eye clinic in identifying patients with an underlying systemic condition.

Histologic and immunohistochemical studies were carried out on four young cattle with diabetes mellitus associated with persistent bovine viral diarrhea (BVD) virus infection. Clinical findings included persistent hyperglycemia, decreased glucose tolerance, glycosuria, polydipsia, and severe emaciation. Macroscopically, multiple erosions and ulcers in the mucosa of upper and lower alimentary tracts and swollen lymph nodes were commonly observed. Erosions and ulcers in the mucosa of tongue, esophagus, and forestomach were represented histologically by necrosis of squamous epithelium with neutrophilic infiltration. In the small and large intestines, villous atrophy and suppurative cryptitis were often observed, along with diffuse infiltration of lymphocytes and macrophages and fibroplasia in the lamina propria. In the pancreas of all cattle, there was a reduction in the number of islet cells, and most of the residual islet cells had hydropic degeneration and a decreased number of secretory granules. Immunohistochemical examination confirmed that these cells were severely degranulated β-cells. In addition, many islets containing necrotic islet cells were observed. These islet cells had increased eosinophilia and shrinkage of cytoplasm, as well as pyknotic nuclei. Inflammation of the islets with mild infiltration of lymphocytes was observed in all pancreatic lobes. In addition, bovine IgG-immunoreactive cells were identified immunohistochemically in the affected pancreatic islets. The BVD virus antigen was not identified in the cytoplasm of the islet cells by immunohistochemical study, although it was identified in the epithelial cells of the small intestine. The histologic and immunohistochemical studies demonstrated that the pancreatic lesions in these animals were similar to those caused by acute insulin-dependent diabetes mellitus (IDDM) in human beings. These findings suggest that IDDM in Japanese Black cattle is an autoimmune disease induced through persistent infection by BVD virus.

Objectives—To examine whether a screening programme for diabetes repeated after an interval of 30 months is worthwhile both in terms of yield of new cases and continued high response rate.Methods—Self testing for postprandial glycosuria was used as it has been shown to have a good response rate, a good yield of cases of diabetes, and a sensitivity and specificity which compares favourably with more expensive and invasive screening methods. A total of 3231 subjects aged 45–70 years in one practice were screened on two occasions 30 months apart. Eighty seven subjects known to have diabetes were excluded. This number included five new patients who had presented since the initial screen; two of whom had moved into the practice, one who screened positive at the initial screen but failed to attend for the oral glucose tolerance test (OGTT), and two subjects who had screened negative, the first presenting 24 months after screening.Results—At repeat screening the return rate was lower than at the first screening (72·5% v 79·2%, P < 0·0001). Glycosuria was detected in 52 subjects (2·3%), at the repeat screening, similar to that at the initial screen. Attendance for the OGTT after a positive screening test was 93·2%. Only six subjects of the 24 with Glycosuria but normal glucose at initial screen were found to have glycosuria again; repeat OGTTs were all normal. Of the remaining 46 subjects, 10 had non-insulin-dependent diabetes mellitus (NIDDM) and five impaired glucose tolerance (IGT). The number of subjects with diabetes was not significantly different from that at the initial screening (0·44% v 0·72%, P = 0·2).Conclusions—Repeat screening after 30 months has a high response rate, similar rate of detection of glycosuria, and a further yield of 0·44% of newly diagnosed cases of diabetes. A screening programme detecting postprandial glycosuria identifies additional diabetic subjects 30 months after a previous screening programme.

OBJECTIVE:To report a case of apparent increased lithium clearance in a patient with persistent hyperglycemia.METHODS:Lithium doses, blood glucose concentrations, and lithium plasma concentrations were evaluated in a patient during a 53-day inpatient admission for exacerbation of bipolar disorder. The lithium dose required to increase the lithium plasma concentration by 0.1 mEq/L was computed from the lithium dose and corresponding lithium plasma concentration. This value was correlated with the blood glucose concentration.RESULTS:A plot of the lithium dose required to increase the lithium plasma concentration by 0.1 mEq/L versus the blood glucose concentration exhibited a direct linear relationship (r2= 0.62). This plot indicates that higher lithium doses are needed during hyperglycemic states compared with euglycemic states to achieve equivalent plasma concentrations.CONCLUSIONS:Glycosuria associated with hyperglycemia induces an osmotic diuresis that increases the renal clearance of lithium, necessitating higher lithium doses to maintain therapeutic lithium plasma concentrations.

A patient with insulin-dependent diabetes mellitus (type 1 diabetes) was admitted to hospital after complaining of general fatigue and weight loss. To control hyperglycaemia, the patient was given a conventional form of insulin subcutaneously twice daily. Although this conventional insulin replacement therapy effectively controlled the symptoms, it did not improve the metabolic state and eventually the patient was re-admitted due to a worsening of his condition. The patient was then given a new preparation of both short- and intermediate-acting forms of insulin, administered twice daily using a new, ‘dial-a-dose’ pen delivery system. Comparative studies of blood insulin dynamics revealed that this new method of delivery resulted in a circadian blood glucose pattern closely approximating normal levels, the complete elimination of subjective symptoms and the normalization of basal insulin secretory patterns. The clear superiority of the new delivery system and the combination insulins in relation to the quality of life of this patient is demonstrated.

A single subcutaneous administration of monosodium aspartate (MSA) to 30 neonatal voles, Microtus arvalis Pallas, induced a diabetes mellitus in 50% of the treated animals in early adulthood. The voles (18 males and 12 females) were weaned at 3 weeks of age and fed pellets for Herbivora and cubed hay. Diabetic voles with glycosuria (nine males and six females) were classified into two groups according to the duration and grade of glycosuria. One group had slight diabetes with glycosuria (+: 0.1%) for 1 week and the other severe diabetes with marked glycosuria (+++: ≧0.5%) for over 4 weeks. Pancreatic islets of diabetic voles ( n = 7) were examined immunohistochemically, light microscopically, and electron microscopically. Blood glucose concentration and tissue content of insulin, glucagon, and somatostatin were also measured. Slightly diabetic voles ( n = 3) had enlarged islets, that, viewed by light microscopy, were characterized by hypertrophy and hyperplasia of β cells with moderate degranulation. No changes were observed in the peripherally located α and β cells; the voles were moderately hyperglycemic, and they had decreased pancreatic insulin content. Severely diabetic voles ( n = 4) that had marked hyperglycemia and almost complete loss of insulin content showed marked vacuolation and degranulation of β cells. In addition, altered distribution of α and β cells from the periphery of the islets to their interior was noted. Ultrastructural examination revealed features compatible with those of hyperfunction of β cells in the slightly diabetic voles and marked degeneration of β cells with glycogen accumulation in the severely diabetic voles. In contrast, α and β cells retained their normal morphologic traits, even in the severely diabetic voles.

On a evalue le rendement clinique de l'examen routinier des urines effectue au moment de l'admission chez un groupe de 515 malades admis dans un hopital psychiatrique. Deux psychiatres de l'hopital ont etudie les dossiers afin de determiner dans quels cas l'examen avait entraine une modification du diagnostic ou du traitement. L'examen routinier a revele des urines anormales pour 40 malades (7.8%), et 17 de ceux-ci (3.3%) ont subi des examens de laboratoire complementaires. Le traitement de sept malades (1,4%) a ete modifie a la suite des nouveaux resultats, mais l'examen des urines de trois d'entre eux etait diagnostique plutot que routinier

The severity of insulin-dependent diabetes mellitus had a marked effect upon the development of myocardial sequelae in the rat. Even with the same degree of hyperglycemia, glycosuria, polydipsia, and polyuria, moderately diabetic animals did not develop the degenerative ultrastructural changes seen in myocardium from more severely diabetic rats. These included decreased cardiocyte size, loss and disorganization of myofibrils, and loss of sarcoplasmic reticulum and transverse tubules. Since hyperglycemia and glycosuria are frequently used as the primary, and often sole, criteria for identifying diabetes in experimental animals, this study demonstrates the need to more specifically define the severity of the disease in studies of the heart.

Diabetic renal disease is associated with increased cardiovascular risk and is one of the leading causes of end-stage renal disease worldwide. A combination of hyperglycaemia and hypertension drives the development and progression of diabetic renal disease, with glomerular hyperfiltration being an early manifestation of the disease process. Sodium- glucose linked transporter 2 (SGLT2) inhibitors represent a novel class of drugs that lower plasma glucose levels through the inhibition of renal proximal tubular glucose uptake and secondary glycosuria. Clinical evidence that SGLT2 inhibitors attenuate glomerular hyperfiltration is complemented by animal data suggesting that these agents can prevent progression of diabetic renal disease. In clinical studies involving patients with type 1 and type 2 diabetes, SGLT2 inhibition reduces glomerular hyperfiltration and appears (albeit in post-hoc and pooled analyses) to reduce urinary albumin excretion. The longer term potential reno-protective effects of this class of drugs are currently under evaluation in large randomised clinical trials.

Amitraz poisoning is a rare disorder characterised by central nervous system and respiratory depression, bradycardia, hypotension, hypothermia, hyperglycemia, vomiting, convulsion and glycosuria. In this study, eight pediatric patients with amitraz poisoning were presented. This study revealed that clinical manifestations of poisoning by oral and dermal route emerged within 30- 120 min and that central nervous system depression which is the most important sign resolved with 8-18 h and others 36-48 h. All cases were discharged as recovered after 48 h. To our knowledge only six cases have been reported in the literature. Because of the limited information in the literature, the cases were reported.

Case report A 58-year-old woman with no significant past medical history, presented to her general practitioner with a 4-week history of lethargy, polyuria and glycosuria. Random glucose of 24.9 mmol/L confirmed the diagnosis of diabetes and in view of marked symptoms, an urgent referral to the clinic was organised. Clinical examination revealed a blood pressure of 227/128 mmHg, ‘plethoric face’ and a ‘Cushingoid appearance’ (figure 1). Routine biochemistry revealed serum potassium of 2.8 mmol/L (normal range 3.5–5 mmol/L), venous bicarbonate of 40 mmol/L (normal range 22–26 mmol/L) and grossly deranged liver function tests. An urgent in-patient admission was arranged in view of the above abnormalities. A random serum cortisol and paired ACTH levels were grossly elevated at 4,047 nmol/L (normal range 110–770) and 366 mu/L (normal range 2–20) respectively. Chest X-ray revealed a right pleural effusion. Chest CT revealed a large right hilar tumour (figure 2) measuring 5 cm diameter with a moderately large right pleural effusion. Abdominal imaging showed multiple liver metastases. Bronchial wall biopsy revealed features consistent with a small cell carcinoma of the lung. The final diagnosis was an ‘ectopic ACTH secreting small cell lung cancer’ presenting with new onset diabetes, hypertension, hypokalaemic alkalosis and Cushing’s syndrome. Subcutaneous insulin was commenced. Chemotherapy was not considered due to her general health. Metyrapone was started in an effort to reduce cortisol secretion but, unfortunately, deterioration was rapid and the patient died within 12 days of admission. Discussion We present an unusual case of ectopic ACTH secreting small cell lung carcinoma presenting initially with classical symptoms of diabetes, elevated random glucose, severe hypertension associated with hypokalemic alkalosis and features consistent with Cushing’s syndrome. Morphological changes of Cushing’s syndrome in such patients with highly aggressive cancer is extremely unusual as the hypercortisolism is acute and patients do not survive long enough for such changes to occur. Not all hyperglycaemia is the same: an interesting case of secondary diabetes

We have studied the relationship between serum glucose and urate in 260 699 men and 214 118 women from Sweden, and 140 084 men and 30 653 women from the UK. We found an increase in mean serum urate with increasing glucose concentrations up to 7·0 mmol/L in men and 9·0 mmol/L in women. Thereafter increasing glucose values were accompanied by a statistically significant decrease in urate concentrations. This fall was particularly marked in younger subjects. We believe this may have important implications for the free radical status of diabetics.

57-year-old deaf male presented to the diabetic clinic with a large ulcer over his right heel which had progressively enlarged over the previous 18 months. Medical help was only sought by his brother when the foot ulcer had reached this advanced state (figure 1). There was no history of thirst or polyuria and no obvious weight loss. The family doctor noted glycosuria and diabetes mellitus was confirmed by a random plasma glucose of 21.7 mmol/L. This unmarried male, a non-smoker and tee-totaller had no documented past medical history. There was no history obtained of macrovascular disease and no subjective features of peripheral neuropathy. The patient was admitted to hospital, from the clinic, for further management of the foot ulcer. Clinical examination revealed evidence of a sensory peripheral neuropathy with loss of vibration and sensation to pin prick and light touch to both knees in a stocking distribution, absent ankle and knee reflexes with no evidence of any motor impairment. The peripheral pulses were readily felt in both feet. The radial pulse was regular at 80 beats per minute, BP 110/60 mmHg; cardiovascular, respiratory and abdominal examination was normal. Examination of both fundi showed extensive hard exudation (figure 2). Investigation showed haemoglobin 13.4 g/dl, white cell count 6.2 x 10 9

was referred to the diabetic out-patient department by his family practitioner. The patient complained of being tired but had no frank hyperglycaemic symptoms. Opportunistic urine testing revealed glycosuria and diabetes mellitus was confirmed by a random plasma glucose of 14 mmol/L. There was no past history of note, there was no relevant drug history and no family history of diabetes. Blood pressure was noted at 140/80 mmHg and total cholesterol was 5.1 mmol/L. The patient smoked 20 cigarettes per day and alcohol intake was 10 units per week. The patient failed to keep his appointment at the out-patient clinic. During the next year, three more appointments were sent and none kept. A personal letter to the patient also failed to get him to the outpatient clinic. The family practitioner was also unsuccessful in getting the patient to attend his own clinic. Two years later ie. three years after the initial referral, the patient presented to the Accident & Emergency Department with ‘an infection in his foot’. Examination revealed gangrene of the foot with pus oozing from the necrotic area (figure 1). There were areas of diabetic dermopathy on both shins (figure 2). The patient was toxic with a fever of 39°C, and clinically he was in diabetic ketoacidosis with Kussmaul (acidotic) breathing. The plasma glucose was elevated at 50 mmol/L, sodium 134, potassium 5.4, bicarbonate 4, urea 12.1 mmol/L respectively with an arterial pH of 6.95. The patient was admitted as an emergency and his metabolic decompensation responded to treatment with intravenous saline followed by dextrosecontaining fluids along with potassium supplements and a lowdose intravenous insulin infusion. Intravenous clindamycin, flucloxacillin and ciprofloxacin antibiotics were administered and an emergency below knee amputation was required some seven days later because of the toxicity caused by severe tissue necrosis. The patient was treated with subcutaneous insulin injections but about six months later his diabetes was controlled satisfactorily by diet alone!

Principle of the method The reaction is as follows: Reagents Phosphate buffer: 0'2moI/L, pH 7·5. Galactose dehydrogenase: 1 mg/mL. Suspension in ammonium sulphate solution, 3· 2 mol/L and EDTA 1 mmol/L (Boehringer, Mannheim, Germany). Colour reagent: 80 mg p-iodonitrotetrazolium violet (INT, Sigma Chemical Co., St Louis, MO, USA) was dissolved in 20 mL of glass distilled water and centrifuged. 200 rng NAD and 5 mg Phenazine Methosulphate (pMS; Sigma Chemical Co.) were added to the supernatant, mixed and stored in a dark bottle at 4°C. This reagent is stable for at least 10 weeks. Galactose standard: 1·0 mmol/L. The average 1·0 h urine volumes obtained from lactose digesters and lactose maldigesters were 295 mL (range 94-580 mL) and 157 mL (range 46-422 mL), respectively. Urine less than 150 mL was diluted to this volume with water to avoid a false positive result due to a concentrated urine sample. All urine samples were assayed for galactose by a commercial kit (Boehringer Galactose kit, Mannheim, Germany) and by our screening method. Blood galactose was measured by the kit method and, based on a blood galactose concentration >0·28 mmol/L, 18 subjects were classified as lactose digesters. 5 The study was approved by the Ethics Committee of the University of Adelaide and the Queen Elizabeth Hospital, Woodville, South Australia.

The lifespan and fertility of albino sand rats were found to be severely reduced in comparison with a laboratory colony of brown sand rats. The albinos were also much more susceptible to diabetes, as judged by their glucose tolerance. In fact, untreated albinos had a higher incidence of diabetic response than coloured sand rats fed a diabetogenic diet. The albino sand rats reproduced poorly because of a reduction in male fertility. Circulating testosterone levels and seminal vesicle weights were reduced in the albinos. It is speculated that the reduction in reproductive capacity is related to diabetes.

For more than 30 years nitrofurantoin has been a widely prescribed and effective agent in the treatment of urinary tract infections. During this time, it has withstood the rigors of constant clinical evaluation and has competed successfully with more recent antibacterial agents. As with many widely used drugs, some serious and potentially hazardous reactions to therapy have been documented. This article reviews and analyzes major reported reactions and interactions from both published and unpublished sources. Incidence rates have been calculated for pulmonary, hepatic, neurological, and hematological responses. Calculated rates of occurrence were very low, and ranged from 0.001 percent of courses of therapy (all types of pulmonary reactions combined) to 0.0007 percent (neurological reactions). Reports on interactions of nitrofurantoin with alcohol, antacids, and oral contraceptives are unfounded and anecdotal. Interactions with nalidixic and oxolinic acids are not clinically significant, and only one case of interaction has been reported with phenytoin. Bioavailability is enhanced by food or propantheline. False positives occur with Benedict's test for urine glucose estimations.

Analytical goals may be defined as those standards of performance required to facilitate optimal patient care. Review of the considerable amount of published work on glucose analyses allows delineation of the following current goals: For plasma glucose: within-laboratory between-batch imprecision — CV≤2·2%; inaccuracy — no bias; linearity − 1 to 28 mmol/L; detection limit − 1 mmol/L; turnaround time − 30 min (in emergency situations). For urine glucose (quantitative): within-laboratory between-batch imprecision — SD ≤0·1 mmol/L; inaccuracy — no bias. for urine glucose (qualitative or semi-quantitative): negative — should be negative; positive — should be positive ± one positive colour block; detection limit − 2·8 mmol/L. Moreover, each laboratory should develop goals for the many pre-analytical factors affecting glucose analyses. While the above goals are not always achieved in current practice, they are attainable and are worthy targets to strive to reach. The general principles discussed here for glucose analyses are applicable to other analytes of interest to the clinical biochemist.

Except when testing for ketones, most people with diabetes monitor their glucose levels by testing blood samples rather than urine samples. For many years, however, urine glucose testing was the standard testing procedure. The history of urine testing as presented in this paper gives one an appreciation of the evolution of glucose monitoring, and demonstrates the importance of urine testing in the past and the part it plays in the present management of diabetes mellitus.

We have previously shown that the antidiabetic property of fenugreek seeds (Trigonella foenum graecum L.) is associated with the defatted seed material which is rich in fibers, saponins, and proteins. In the present work this defatted preparation was divided into two subfractions: subfraction "a" which contains the testa and endosperm and is rich in fibers (79.6%); and subfraction "b" which contains the cotyledons and axes and is rich in saponins (7.2%) and proteins (52.8%). We investigated the effects of each subfraction on hyperglycemia and the levels of pancreatic hormones when chronically administered to alloxan-diabetic dogs. Each subfraction was studied separately and was given to the dogs per os (mixed with the two daily meals), in addition to the insulin treatment (which was kept the same throughout the experiment) for a period of 21 days. The addition of subfraction "a" to insulin treatment resulted in a clear decrease of hyperglycemia and glycosuria accompanied by a reduction of the high plasma glucagon and somatostatin levels in diabetic dogs. The treatment also decreased the hyperglycemic response to the oral glucose tolerance test. In contrast the chronic administration of subfraction "b" had no effect on hyperglycemia or on the levels of pancreatic hormones in diabetic dogs. Our results show that the antidiabetic properties of fenugreek seeds are contained in the testa and endosperm. Although this subfraction is rich in fibers (high viscosity; 115 cP), it is not possible to exclude the existence of one or more unknown active pharmacological compounds in this subfraction of the seed.

The effect of ten new β-lactam antibiotics (cefoperazone, cefotaxime and its metabolite desacetylcefotaxime, ceftazidime, ceftizoxime, ceftriaxone, aztreonam, azlocillin, mezlocillin, piperacillin, and ticarcillin) on the accuracy of Clinitest, Diastix, and Tes Tape determinations of glycosuria was investigated. Solutions of each of the antibiotics were prepared in urine over a range of clinically obtainable drug concentrations. Urine samples from a healthy subject were used to prepare simulated diabetic urine by adding dextrose to achieve concentrations of 0.5%, 1%, and 2%. With penicillin derivatives, falsely elevated Clinitest readings generally were observed at lower glucose concentrations. When no glucose was present, cephalosporins and the monobactam, aztreonam, gave a dark green-black color that could only be interpreted as 0% on the Clinitest color chart. At higher urine glucose concentrations (1% and 2%), no interaction with Clinitest could be demonstrated, with the exception of a few falsely reduced readings. All urine solutions containing β-lactam antibiotics were estimated accurately by both Diastix and Tes Tape. The unpredictability of the Clinitest-β-lactam antibiotics interaction should discourage the use of this urine glucose test in patients who receive these drugs. The glucose-oxidase tests, Diastix and Tes Tape, may be used as qualitative tests for glycosuria in patients treated with β-lactam antibiotics.

Sulphonylureas are still prescribed in increasing amounts in the UK (Statistics and Research Division, DHSS, personal communication) despite the suggestion from the Universities Group Diabetic Program trial (1970) that their use may be associated with an increased risk of cardiovascular death. Tolbutamide, the first of the sulphonylureas still in common use, has a half-life of only five hours and is usually taken in two or three daily doses. The half-life of chlorpropamide, which is not metabolized by the liver, is 36 hours and its use may lead to prolonged hypoglycaemia particularly in the elderly and those with renal impairment (Schen & Benaroya 1976). Glibornuride has been widely used on the continent for several years, but only recently became available in the UK. This compound is rapidly absorbed from the gut and inactivated by the liver to give a half-life of eight hours. A trial was set up to examine the clinical acceptability of glibornuride and to confirm that like other sulphonylureas it leads to an increase in insulin secretion (Perkins et al. 1977).

Glucose intolerance preceding pulmonary disease in a child with cystic fibrosis is de scribed. After glucose intolerance was con trolled with tolbutamide, the pulmonary infec tion resolved. Early recognition and treatment of "diabetes" in children with cystic fibrosis is emphasized.

1 Urine was collected from 289 inhabitants of a cadmium-polluted quarter of Stadskanaal. The excretion of cadmium, protein, beta-2-microglobulin and glucose were determined. After being divided according to sex and to smoking habits, the results of the inhabitants were compared with those of 293 controls. 2 In inhabitants as well as controls, cadmium excretion was age-dependent. Cadmium excretion in females increased faster with age than in males. 3 In male-smoker controls, cadmium excretion was significantly higher (p < 0.001) than in male-non-smoker controls. 4 In male-non-smoker inhabitants, cadmium excretion (p = 0.05), protein excretion (p 5 For some categories, living in the polluted area was associated with an increased cadmium excretion in urine and a slight difference in renal function, possibly related to a difference in cadmium body burden. It was concluded that, considering the actual values of each parameter, the observed differences were not relevant in terms of potential health hazards.

Questionnaires were sent to 550 female patients aged 13 to 45, with insulin-dependent diabetes to determine the prevalence of eating disorders in this population. Seventy percent of the question naires were returned and analyzed. One percent of respon dents met criteria for lifetime prevalence of anorexia nervosa, 16. 2 % for lifetime prevalence of bulimia, and 4.9% for induced glycosuria. Contrary to previous studies, the prevalence of bulimia and anorexia was within the range identified in the general population, although at the upper end of the range. The medical risks incurred by women with diabetes who have eating disorders, however, are substan tially greater and warrant attention. The incidence of induced glycosuria is a significant problem for diabetes educators and health care providers working with women who have discovered a dangerous but effective way to lose weight.

SummaryThe toxic effects of 3 degradation products of tetracycline: 4-epitetracycline, anhydrotetracycline, and anhydro-4-epi-tetracycline were studied in rats and dogs. Anhydro-4-epi-tetracycline was the only degradation product which caused abnormal urinary findings similar to the Fanconi-type syndrome observed in man after ingestion of improperly stored tetracycline preparations. Severe, nephrotic changes were found in the kidneys of rats after very large oral doses (1000 mg/kg/day) and in dogs after intravenous doses of 10 and 20 mg/kg respectively on successive days.

A relation of the anterior pituitary to carbohydrate metabolism has often been suspected on the basis of the frequent occurrence of hyperglycemia and glycosuria in acromegaly, and of anatomical changes in the anterior pituitary in diabetes mellitus, but such a connection was not indicated experimentally until Houssay and Biasotti1 showed that pancreatic diabetes could be prevented in toads by removal of the anterior pituitary. Subcutaneous implantation of anterior pituitary in such depancreatized toads re-established the diabetes. They were unable to show a similar relation in mammals either by gland implantation or by injections of anterior pituitary extracts, although depancreatized and hypophysectomized dogs survived longer and showed milder diabetes than did depancreatized controls2. Evans, Meyer, Simpson, and Reichert3 reported observations in which they produced glycosuria and polyuria in 2 of 4 dogs by daily injections of the growth hormone fraction of anterior pituitary extracts for 8 or 9 months....

SummaryGlutathione, when injected into normal animals which had been force-fed a high carbohydrate diet, induced glycosuria. The amount of glycosuria decreased with increasing adaptation to the high carbohydrate diet and after feeding the diet for 2 months, glutathione produced insignificant effects. By contrast the injection of glutathione into cortisone-diabetic rats caused a marked (in some cases up to 10 fold) increase in glycosuria which has been observed even after 3 months of the high carbohydrate diet. Cysteine and ascorbic acid were also studied. Glutathione potentiates the diabetogenic effect of cortisone. The mechanism of this potentiation has been discussed and its possible significance in the treatment of rheumatic disease has been suggested.

SummaryJensen sarcoma caused a striking decrease in the glycosuria of extensively depancreatized male rats in the presence of the adrenal glands and in adrenalectomized-depancreatized rats treated with adrenal cortex extract. There was an accompanying decrease in the level of urinary nitrogen. The rate of tumor growth was inversely related to the severity of pancreatic diabetes.

SummaryCastrated female rats, with surgical ablation of 95% of the pancreas and maintained under forced feeding were injected with stilbestrol.In some of these animals, immediately after stilbestrol administration, a transitory stage lasting for about one month, with an increase of the blood sugar level and glycosuria values was olbserved, followed by a permanent protective action in all the stilbestrol treated rats with normal values in blood sugar and glycosuria, in contrast with the increase of these values observed in non injected controls.

The diffuse distribution of the pancreas in the rabbit and the attending problems of surgical removal have prevented the study of pancreatic diabetes in this animal. In fact, it has been pointed out that “in rabbits the operation itself is impossible, because of the spread-out condition of the pancreas.”1 However, a method for complete pancreatectomy is presented here together with data pertaining to insulin requirements, glycosuria, blood sugar levels, etc.The pancreas in general, is a thin sheet of tissue lying in the meso-duodenum with one large mass on the right between the portal vein and the vena cava and another mass in the mesentery of the spleen.At operation it is essential to use a Beebe binocular loupe to pick up the small fragments of pancreas which break off and to prevent injury to small intestinal blood vessels. For rabbits of about 2 kilos the anesthetic used is 1 cc. of nembutal intravenously, 0.2 cc. of 1% atropine subcutaneously and sufficient ether at the beginning to allow opening of ...