Sodium glucose Co transporter 2 (SGLT2) inhibitors: a new sword for the treatment of Type 2 Diabetes Mellitus

The low affinity sodium glucose cotransporter (SGLT2) plays a major role in physiology of glucose re-absorption from proximal part of kidney. Almost all glucose excreted through glomerular filtration, is re-absorbed via SGLT2 until blood glucose level reaches to its threshold value for glucose excretion i.e. - 180mg/dl. Increasing the glucose excretion by inhibiting the SGLT2 is the novel approach for the treatment of diabetes. Safe and normal life of patients having familial renal glucosuria due to SLC5A2 gene mutation is accelerating the development of SGLT2 inhibitors. Weight loss and very low risk of hypoglycemia are the potential benefits of these inhibitors. There are number of molecules in this class under the stage of development.

Modern insulin therapies

Insulin therapy is essential in the management of type 1 diabetes, and extremely useful in the management of type 2. There are a number of established treatment strategies, including basal-bolus, twice-daily, and insulin/tablet combinations. There are currently emerging a number of new insulin analogues - both very rapid-acting and truly once-daily, and they potentially have a great deal to offer to the management of our patients. Current development is also focused on the possibility of giving insulin via a route in which injection could be avoided. At present, however, these are still a number of years away from availability (AU)

Peripheral occlusive arterial disease in diabetic clinic attendees

Peripheral occlusive arterial disease occurs with a greater frequency in the diabetic population than in the general population. It can have debilitating effects and so early detection and intervention are important. The aim of this study was to investigate the prevalence of peripheral occlusive arterial disease (POAD) among a sample of diabetic patients attending the out-patient clinic at the University Hospital of the West Indies (UHWI), Mona. A sphygmomanometer was used to measure arm and ankle blood pressures in 80 diabetic patients, and the ankle-brachial systolic pressure index (ABI) was determined. The presence or absence of peripheral pulses was detected with the Multi-dopplex (model 1). POAD was defined by the absence of one or more peripheral pulses and/or an ABI < 0.09. Of the 80 diabetic patients examined, 18 (22.5 percent) were found to have POAD. Seventy-eight percent of diabetics with POAD had the disease in both legs. Intermittent claudication was diagnosed in 27.7 percent of patients with POAD. A significantly larger proportion of diabetics with POAD were hypertensive and/or neuropathic (p < 0.05). The results suggest that serious attention should be given to the quantitative screening for POAD in the diabetic patients attending the clinic at the UHWI (AU)

A survey of knowledge, attitude, practice and perception of diabetics on insulin therapy in St. Thomas, Jamaica

This cross-sectional survey of diabetics on insulin therapy sought to identify the level of knowledge of patients on insulin regarding diabetes and insulin therapy and to ascertain the perception, attitudinal and behavioural practices of these clients as it relates to insulin therapy and self administration in St. Thomas, Jamaica. A total of 107 clients were interviewed using a structured questionnaire which was administered as an interview schedule. Three focus group discussions were also conducted. Knowledge was high in the area of responses to whether or not insulin lowers the blood sugar, what is to be done if the respondents felt bad after taking insulin and also where insulin is injected. The highest percentage response to the question assessing knowledge was found in clients who used insulin between 5-9 years. There was poor knowledge in the questions addressing identification of insulin by type brand and in addition most persons felt it was alright to miss insulin for a day. This could influence the practices being carried out by the diabetics and quite likely place them at high risk for hypoglycaemia and hyperglycaemia. Most respondents had a fair attitude towards insulin therapy when compared to the length of use of insulin. Most persons also showed a fair attitude towards their treatment particularly those with over ten years of use. The role of health education and other types of support for diabetics on insulin therapy were identified among factors that could facilitate better practices. Keen attention should be paid to the socio economic environment as it impacts readily on these clients especially the elderly and the indigent in their ability to care for themselves.(Au)

Hormonal counterregulation of hypoglycaemia in IDDM patients during and after pregnancy

An increased frequency of hypoglycaemic events is commonly observed during pregnancy in intensively treated IDDM patients. It has been speculated upon whether this is due in part to impairment of the hormonal counterregulation. The main aim of this study was to clarify if the hormonal response to hypoglycaemia is modified during pregnancy. Therefore we assessed plasma levels of catecholamines, GH and cortisol as well as subjective symptoms and cognitive functions during a hyperinsulinaemic, hypoglycaemic clamp in the third trimester of pregnancy and 6-12 months after delivery. Venous samples for the analysis of hormones and free insulin were taken every 15 minutes and symptoms of hypoglycaemia were recorded on a visual analogue scale at 30-min intervals. Cognitive functions were studied by a psychological test system at normoglycaemia and at hypoglycaemia. The Wilcoxon signed rank test was used for statistical calcuations. The levels of noradrenaline (mean at hypoglycaemia pregnant 2.30, and non-pregnant 2.44 nmol/l, n.s.) increased the same way on the two occasions, while the adrenaline response was some what higher in the pregnant state (2.09 vs 1.66 nmol/l non-pregnant, p<0.05). The cortisol increase was faster and more pronounced during pregnancy (mean increase 327 vs 130 nmol/non-pregnant, p<0.0001) while the increase in GH was higher in the non-pregnant state (mean increase 23.6 vs 8.7 æg/l pregnant, P<0.0001). We conclude that the present study does not, with the exception of GH, give evidence that pregnancy per se diminishes the counterregulatory hormones response (AU)

Managing hypoglycaemic reactions - abstract

Hypoglycaemia is the major complication of insulin treatment of IDDM and sulfonylurea therapy of NIDDM. The presentation and management of hypoglcaemia in each of these therapuetic situations is somewhat different. Intensive insulin therapy of IDDM results in a significantly increased risk of hypoglycaemia as shown (in the Table given - which is taken from the recently published Diabetes Control and Complications Trial). Protection against hypoglycaemia is mediated by the counter-regulatory system. Hypoglycaemia (blood glucose < 60 mg/dl) is recognised by centres in the brain which stimulate glucagon, catecholamines, cortisol and growth hormone secretion. Investigative studies indicate that increased glucagon secretion normally is the most important factor in alleviating hypoglycaemia. Increased epinephrine and non-epinephrine contribute to the alleviation of hypoglycaemia while cortisol and growth hormone play a permissive role. Correction of hypoglycaemia occurs primarily by an increase in hepatic glucose production. In IDDM patients, glucagon secretion in response to hypoglycaemia diminishes and disappears after about 5 years of disease. These individuals rely primarily on increased catecholamine secretion to ameliorate hypoglycaemia. Autonomic neuropathy creates a major problem since it results in reduced ability to respond to hypoglycaemia due to dysfunction of the sympatho-adrenal axis. Prevention of hypoglycaemia focuses on adequate self-blood glucose monitoring and careful attention to meal timimg and insulin administration. Excercise and severe physical activity must be accompanied by either alterations in insulin administration or food consumption. The mainstay of hypoglycaemia treatment in IDDM patients is oral administration of carbohydrates. The initial dose should be 15 gm and should be in hard form if possible. Excessive carbohydrate will result in severe hyperglycaemia and should be avoided. In the non-hospital setting when the individual cannot be given oral carbohydrate, an IM injection of 1 mg glucagon is useful in restoring blood glucose levels. In the hospital setting intravenous administration of 50 per cent glucose (25 gm) will be most rapid and effective. Sulfonylurea-induced hypoglycaemia presents a somewhat more complicated problem. Mild to modest hypoglycaemia requiring food or carbohydrates ingestion is relatively common (as many as 20 per cent of patients in a 6-month period). Severe hypoglycaemia occurs quite infrequently but is associated with significant mortality. Estimated prevalence is 0.25 per 1000 treatment years with a mortality around 5 per cent. Most severe hypoglycaemia occurs when long-acting sulfonylureas are administered to elderly patients with renal or cardiovascular disease. Hypoglycaemia can be minimized by strong starting therapy with very low doses and increasing the dose slowly. Treatment of severe sulfonylurea-induced hypoglycaemia requires (1) rapid recognition, and (2) administration of 25 gm of 50 per cent glucose IV followed by a continuous 5 or 10 per cent glucose infusion with blood glucose monitoring for a minimum of 36 hours. Intractable hypoglycaemia may require cortisol, diazoxide or somatostatin to be administered in addition to the glucose treatment (AU)

Toxic hypoglycemic syndrome Jamaica, 1989-1991

In January and February 1991, the health officer in the parish of St. Ann, Jamaica, received reports of eight persons with Toxic Hypoglycemic Syndrome (THS), an illness associated with consumption of unripe ackee fruit and, possibly, renta yam; two cases were fatal. On July 25, the Jamaican Ministry of Health (JMH) contacted the Centers for Disease Control (CDC) for assistance in investigating the continuous occurence of THS; the collaborative JMH and CDC epidemiologic investigation focused on characterizing the epidemiology of THS in Jamaica and assessing the role of ackee fruit, renta yams, and other factors (AU)

Hypoglycaemia in chronic renal failure

Persistant symptomatic hypoglycaemia developed in a 26-year-old woman with chronic renal failure. Several factors, including the use of sulfametethroxaole, recent peritoneal dialysis, and poor nutrition may have combined with defective glycogenosis and gluconeogenesis present in chronic renal failure to play a role in its aetiology. Increased awareness of this condition is necessary because chronic renal failure is common in the Caribbean. (AU)

One hundred cases of hypoglycaemia - abstract

The purpose of this paper is to report a review of the aetiology, clinical features and differential diagnosis in 100 cases of hypoglycaemia seen at the General Hospital, Port-of-Spain. A retrospective study was made of 100 admissions with a final diagnosis of hypoglycaemia. Only cases with a blood sugar of 50 mgm percent/2.77 mmol/1 or less, or in which there was a definite response to intravenous glucose, were included. Although the majority of cases occurred in association with diabetes mellitus, at least 19 percent were in patients with excess alcohol intake. There is often a delay in diagnosis; in 11 cases the delay was 12 hours or more, and in 3 over 24 hours. A wide range of clinical features included bad feelings, fits, hemiparesis, dysphasia, confusion, strange or aggressive behaviour, neck stiffness and unequal pupils. The differential diagnosis included encephalitis, meningitis, epilepsy, subdural haematoma, poisoning, hypertensive encephalopathy, psychosis and diabetic coma. In 39 cases a diagnosis of CVA was made. Hypoglycaemia may produce clinical features of psychiatric, neurological and neurosurgical disease and is an important differential diagnosis to be considered in cases with disturbance of consciousness. The diagnostic and therapeutic use ofi.v. dextrose in advocated, in order to avoid missing hypoglycaemia which is an eminently treatable condition , and which if untreated may produce permanent neurological deficit and death (AU)

Toxic hypoglycemic syndrome - Jamaica, 1989-1991

In January and February 1991, the health officer in the parish of St. Ann, Jamaica, received reports of eight persons with toxic hypoglycemic syndrome (THS), an illness associated with consumption of unripe ackee fruit and, possibly, renta yam; two cases were fatal. On July 25, the Jamaican Ministry of Health (JMH) contacted CDC for assistance in investigating the continued occurrence of THS: the collaborative JMH and CDC epidemiologic investigation focused on characterizing the epidemiology of THS in Jamaica and assessing the role of ackee fruit, renta yams, and other factors. (AU)

The effect of bixa orellana (annatto) on blood sugar levels in the anaesthetized dog

The fruit of Bixa has red-coated seeds. This red coat was extracted with chloroform and the solution evaporated to dryness. The dried product was sparingly soluble in oil, and a saturated solution (4 gm per 100 ml) produced non-insulin mediated hypoglycaemia and insulinopenia. A 13.4 gm per 100 ml absolute alcohol solution produced hyperglycaemia. The potential therapuetic value of this extract supports its detailed investigation (AU)

Sulphonylureas and hypoglycaemic emergencies - abstract

Adult admissions to Queen Elizabeth Hospital over the last three years with a discharge diagnosis of hypoglycaemia were reviewed. There were 55 such admissions among 49 patients (23 males and 26 female). Nine were related to ethanol excess (all males), 39 to diabetic treatment and one remained unexplained. Of the diabetic 10 were taking insulin and 29 oral agents. These were chlorpropamide alone (22), daonil alone (5), chlorpropamide plus daonil (1) and unidentified (1). Only six patients received metformin but in combination with one of the above. Five patients had a history of diagnosis and treatment for diabetes mellitus of less than one week and all were on sulphonylureas. Two patients were admitted twice and one five times for chlorpropamide hypoglycaemia. The mean age was 66 (range 18 to 86), while the mean of patients on oral agents was 70(P>0.05). Thirty-five (71 percent) presented with loss of consciousness, 7(14 percent) with disorientation, four with a stroke, one with a "transient ischaemic attack" and one with a fit. Patients fell obviously into short and long stay categories, i.e 19 were discharged in three days or less, while 18 remained in hospital for more than a week. Five of these died (overall mortality 10 percent) four with a permanent stroke. Two were chlorpropamide-related, in two the drug was unidentified and one was insulin-related. Four patients on sulphonylureas had prolonged hypoglycaemia after hositalisation, with low blood sugars and hypoglycaemic syndromes documented between days 2 and 4. These results indicate that hypoglycaemia is a relatively common cause of emergency hospitalisation in Barbados and that 60 percent are sulponylurea-related. 30 percent of these had renal impairment, but this did not differ significantly from renal impairment in the whole group (34 percent). More important risk factors appeared to be old age, poor nutrition and excessibe sulphonylurea in recently diagnosed elderly diabetics. There is need for a short acting sulphonylurea such as tolbutamide in local formularies and for greater emphasis on diet as first line treatment in such patients (AU)

Fasting glucose production in the smaller of twins with epinephrine-deficient hypoglycemia

The possibility that insufficient glucose production or availability of gluconeogenic substrates could account for fasting hypoglycemia was investigated in three children with epinephrine deficiency. Each had been born the smaller of discordant identical twins, and the unaffected twins served as controls. Fasting plasma glucose production was measured by constant infusion of U-[13]C-glucose under steady-state conditions and was compared with availability of potential glucose sources estimated from respiratory calorimetry and excretory nitrogen. The average rate of glucose production was 2.6 mg/kg/min in the affected twins after they became symptomatic and 2.9 mg/kg/min in the control twins after comparable fasting. Plasma alanine was lower in the affected twins during this interval (average: 0.11 mM versus 0.16 mM), but not earlier prior to decreased plasma glucose; alanine correlated with plasma glucose in a similar way in both groups (r = 0.77). Plasma urea production was 0.30 versus 0.15 mg urea N/kg/min. The calculated availability of potential gluconeogenic amino acids was 1.2 versus 0.6 mg/kg/min. Availability of glycerol, estimated from respiratory calorimetry was 0.4 mg/kg/min in both groups. In two of the twin pairs, net oxidation of carbohydrate (glycogen) was, by design, relatively small under these conditions (0.1 and 0.4 mg/kg/min in the affected and control twins, respectively). Gluconeogenesis therefore accounted for the majority of glucose production. The unaccounted remaining major gluconeogenic source is assumed to be recycled substrates from unoxidized pyruvate. Infusion of excess alanine in these two pairs increased plasma glucose and glucose production similarly in both the affected and control twins. This change was associated with an abnormally large increase in plasma alanine. In the third twin pair, net oxidation of carbohydrate was greater in the affected twin (1.8 versus 1.3 mg/kg/min) and possible glucose sources exceeded total glucose production during hypoglycemia. Earlier during fasting, net oxidation of carbohydrate in this twin was 5.8 mg/kg/min versus 3.1 mg/kg/min in the control. Plasma glucose production measured simultaneously was 4.3 versus 3.8 mg/kg/min, being less than the rate of carbohydrtae oxidation in the affected twin. It is concluded that the abnormal fasting metabolism observed in these children with decreased epinephrine was not primarily a consequence of deficient glucose production or lack of potential gluconeogenic substrates. Initial persistent oxidation of glycogen and subsequent increased utilization of protein during hypoglycemia indicate failure to conserve these limited net sources of pyruvate(AU)

Fasting energy utilization in the smaller of twins with epinephrine-deficient hypoglycemia

The possible role of epinephrine deficiency in abnormal utilization of energy sources during fasting was investigated in three pairs of discordant identical twins with recurrent fasting hypoglycemia. The hypoglycemic twins, ages 2, 8 and 9 years, each had beens smaller at birth. Defective epinephrine responsiveness to hypoglycemia was established by administration of 2-deoxyglucose, 50 mg/kg, i.v. In the control twins, this resulted in a rapid increase of plasma glucose (+39 mg/100 ml), free fatty acids (+0.3 mM), and urinary epinephrine (+224 ng/mg creatine). These changes did not occur in the affected twins. Fasting metabolism in the epinephrine-deficient twins was compared to the unaffected twins as controls. Oxidation of carbohydrate and fat were estimated from hourly measurements of oxygen consumption and carbon dioxide production, and utilization of protein was determined from nitrogen excretion. PLasma glucose decreased more rapidly in the affected twins during the 8 hours prior to appearance of symptoms. During this period, carbohydrate was oxidized more rapidly than in the controls (average: 3.1 versus 1.7 mg/kg/min). Plasma á-hydroxybutyrate and free fatty acids was frequently less in relation to glucose. Symptoms occurred when the sum of both glucose and á-hydroxybutyrate was lower than in the controls. Urinary epinephrine excretion increased from an average baseline of 18 to a maximum of 134 ng/mg creatinine in the control twins. The average maximum urinary epinephrine reached in the deficient twins was only 51 ng/mg creatinine, in spite of lower glucose. Plasma insulin decreased in relation to glucose below 40 mg/100 ml in the control twins (r = 0.65), but this did not occur in the deficient twins (r = -0.38). Cortisol and growth hormone responses were similar in the two groups. THerefore, the consequences of inability to increase epinephrine when availability of glucose became acutely limiting were inappropriate persistent oxidation of carbohydrate, decreased circulating alternate substrates from fat, and lack of suppression of insulin. (AU)

Reye's syndrome - a case report

A single case fulfilling the clinical and pathological criteria of Reye's syndrome is reported. The possible aetiology of the syndrome, the diferential diagnosis with special reference to toxic hypoglycaemia induced by ackee and renta yams, and the treatment of the disease are discussed. This report represents to our knowledge the first case of Reye's syndrome thus documented in Jamaica (AU)