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Bioenergetics in clinical medicine. XI. Studies on coenzyme Q and diabetes mellitus.

The activity of the succinate dehydrogenase-coenzyme Q10 reductase from 120 diabetic patients was significantly lower (P less than 0.001) and the per cent deficiency was significantly higher (P less than 0.001) than that of the controls. The diabetes of 37 patients was controlled by diet; the enzyme activity was lower (P less than 0.001) and the deficiency was higher (P less than 0.02) than for controls. In decreasing effectiveness, Dymelor, Glyburide, Phenformin and Tolazamide inhibited the COQ10-enzyme, NADH-oxidase. Tolbutamide, Glypizide, and Chlorpropamide were noninhibitory to succinoxidase and NADH-oxidase. Patients receiving Tolazamide and Phenformin showed a higher incidence (P less than 0.001 to P less than 0.05) of COQ10-deficiency than patients controlled by diet or normal controls. Certain diabetic patients controlled by diet may have a deficiency of COQ10 which may be enhanced by the inhibition by certain commonly used antidiabetic drugs of COQ10-enzymes. A deficiency of COQ10 in the pancreas could impair bioenergetics, the generation of ATP, and the biosynthesis of insulin.

Adult↗

Comparison of capillary electrophoresis with HPLC for diagnosis of factitious hypoglycemia.

BACKGROUND: The diagnosis of "factitious hypoglycemia" is essentially based on the disclosure of hypoglycemic agents in blood or urine. The aim of this study was to evaluate the performance of capillary electrophoresis (CE) as a quantitative method for determination of chlorpropamide, tolbutamide, glipizide, gliclazide, and glibenclamide in serum. METHODS: Serum samples (1 mL), with internal standard added, were purified by solid-phase extraction on OASIS(TM) HLB cartridges (Waters), dried under reduced pressure, and reconstituted with 30-60 microL of acetonitrile:H(2)O. Analysis was carried out by micellar electrokinetic capillary chromatography in 5 mmol/L borate, 5 mmol/L phosphate, 75 mmol/L sodium cholate, pH 8.5, containing 25 mL/L methanol. Separation was accomplished in a 20 cm x 50 microm (i.d.) silica capillary at 25 degrees C and a constant voltage of +10 kV. Pharmacokinetics of gliclazide (80-mg tablet) in a diabetic patient were assayed by both HPLC and CE. Two hypoglycemic patients positive by HPLC analysis for unreported gliclazide and tolbutamide overdose were also screened by CE. RESULTS: Separation of six drugs (including the internal standard) was accomplished in 5 min plus 5 min rinsing. The between-day CV of the ratio of the areas of the sulfonylurea drugs to internal standard was <1% (n = 10). Linearity (r(2) > or =0.998) and recovery (> or =80%) were good for all sulfonylurea drugs tested. Pharmacokinetic curves for gliclazide by CE and HPLC were superimposable. CE analysis confirmed the HPLC diagnosis of surreptitious abuse of gliclazide and tolbutamide. CONCLUSION: CE is a useful tool in the clinical chemistry and toxicology laboratory for drug monitoring and pharmacokinetic investigations.

Adult↗

Effect of acarbose on glycemic control, serum lipids and lipoproteins in type 2 diabetes.

OBJECTIVE: To assess the efficacy of acarbose monotherapy during 12-weeks treatment on the fasting glycemic level, lipid and lipoproteins profiles, in patients with type 2 diabetes mellitus. SETTING: Type 2 diabetics were selected from out patient department of Baqai Diabetes and Endocrine Centre, and one other diabetic clinic of Karachi, during 1996-97. DESIGN: A prospective intervention trial, and a 10 days screening period with a follow-up of 12 weeks. METHODS: Forty-four patients (36 men and 8 women, mean age 55.09 +/- 1.72 years) were included of whom 25 (56.81%) patients were previously treated with diet alone, 11(25%) with diet and glibenclamide, 5(11.36%) with diet and gliclazide, and 3(6.81%) with diet and chlorpropamide, more than at least 3 months known duration of diagnosed type 2 diabetes, body mass index (BMI) 23.69 +/- 0.49 kg/m2, were insufficiently controlled on diet alone, or diet plus sulfonylureas, were studied. The dosage of acarbose was started with 50 mg t.i.d with each meal, if necessary, was titrated upward on subsequent visits to 100 mg t.i.d with each meal, based on tolerability and efficacy. Fasting blood glucose, lipid and lipoprotein profiles were determined at the baseline and at the end of the study. RESULTS: Acarbose treatment was associated with significant reduction in fasting blood glucose from (mean +/- SE) 173.89 +/- 3.89 mg/dl at day 0 to 161.29 +/- 3.41 mg/dl at day 90 (P < 0.01). The serum total triglyceride level was (mean +/- SE) 188.85 +/- 5.91 mg/dl at entry, and was also significantly decreased to 158.57 +/- 4.48 mg/dl at day 90, this reduction was found statistically significant (P < 0.01). Whereas very-low density lipoprotein cholesterol reduced significantly from 33.08 +/- 1.09 mg/dl at day 0 to 31.02 +/- 0.95 mg/dl at day 90 (P < 0.01). Acarbose had no significant effect on serum total cholesterol, low-density lipoprotein cholesterol, and High-density lipoprotein cholesterol concentrations. Almost, all adverse experiences, as reported by patients on acarbose, were related to the digestive system and included diarrhea, flatulence, bloating and nausea. Most symptoms were of mild to moderate intensity and tended to improve with time. Overall, acarbose was well tolerated and the adverse experience profile was clinically acceptable. CONCLUSION: In type 2 diabetic patients, acarbose as monotherapy for 12 weeks resulted in beneficial effects on glycemic control, fasting blood glucose, mean serum total triglyceride and very-low density lipoprotein cholesterol decreased significantly. Perhaps attainment of normoglycemia on a long-term basis would result in more normal lipid and lipoprotein levels. Furthermore use of acarbose can be considered as a useful alternative in such type 2 patients, if they are difficult to control with diet alone or diet plus sulfonylureas (JPMA 50:152, 2000).

Acarbose↗

New trends in diabetes management.

The box of syringes, pile of needles, and refrigerator or ice chest with insulin remain good clues to the presence of diabetes in your patient. EMS providers must recognize that not all diabetics--even type I, insulin-dependent diabetics--carry this paraphernalia. The insulin-delivery system may be the size of a beeper, a small pen or even an inhaler device. If the patient has an alteration of consciousness, the astute provider will search for these clues, check the blood glucose and treat appropriately. The availability of four classes of oral diabetic agents allows many type II diabetics to be treated without the use of insulin. EMS providers may see these agents used alone, in combination with other oral agents or with insulin. Important points to remember include the possibility of hypoglycemia with the sulfonylureas, lactic acidosis with metformin, and liver failure with the thiazolidinediones. The sulfonylureas and chlorpropamide, specifically, may provoke an Antabuse-like reaction when the patient drinks alcohol.

Blood Glucose↗

[Loeffler syndrome and Mycoplasma pneumonitis. A case report].

We describe a clinical case of Loeffler syndrome occurred in a famale aged 13 years. This syndrome is characterized by fleeting pulmonary infiltrates and blood eosinophilia until 70%. Patients usually are only mildly ill or asymptomatic and recovery occurs from few days to some months. Principle causes are: a) mycetes as Aspergillus; b) helmints as Toxocara, Ancylostoma, Trichinella, Ascaris, Strongyloides, Schistosoma; c) chemical agents such as penicillin, para-aminosalycilic acid, hydralazine, nitrofurantoine, chlorpropamide. This girl came to our observation in good general conditions with murmur reduction on the thorax left side, marked peripheral eosinophilia (E 55% of 6100 white blood cell), right pulmonary infiltrate on RX and CT scan. One month before she had fever, treated with amoxycillin and clavulanic acid. Mantoux, Prick tests for main inhalant allergenes, ACE, repeated stools and seric investigations for parasites, mycetes and organisms, were negative except for IgM anti-Myco-plasma antibodies. Broncholavage showed marked eosinophilia. Smear didn't show any blast. The girl recovered in about 40 days (E 4.1% of 8500 WBC, RX negative). Our hypotesis is a causative role of amoxycillin in inducing the syndrome, even if this is a rare event, with an overlapping of a Mycoplasma infection.

Adolescent↗

Chronic diseases management in the Jamaican setting: HOPE worldwide Jamaica's experience.

The prevalence of hypertension and diabetes in Jamaica is very high. Hypertension is present in 3 out of 10 Jamaicans over the age of 30 years while the prevalence of diabetes mellitus varies between 13% and 18% for Jamaicans over 15 years. HOPE worldwide Jamaica is a 7-year-old private voluntary organization that collaborates with the government of Jamaica to provide a mobile medical service to poor rural communities. The records between January 1999 and December 1999 of 1091 chronic disease patients aged > 30 years were reviewed. The average recorded age of the patients was 64 years and 82% among them were females. 60% had hypertension, 16% had diabetes and 24% had both diabetes and hypertension. There were 2390 visits for hypertension, with an average of 2 visits per patient. 34% of patients had a blood pressure of < or = 140/90 mmHg while 43% had a blood pressure < 160/95 mmHg. Compliance was defined as daily consistency in taking prescribed medication. 44% of the patients with hypertension were non-compliant at the time of their visit. Antihypertensive treatment included thiazide diuretics (65%), reserpine (50%), angiotensin converting enzyme (ACE) inhibitors (30%) and alpha-methyldopa (5%). There were 1122 visits for diabetes, with an average of 2 visits per patient. Among the diabetic patients 23% were controlled to a fasting blood glucose (FBG) level of less than 6.7 mmol/l and 38% to below 8 mmol/l. 30% of the diabetic patients were non-compliant at the time of their visit. The most frequently used oral hypoglycaemic agents were metformin (78%), glyburide (43%) and chlorpropamide (30%). 14% of the diabetic patients were on treatment with insulin: insulin 70/30 (12%) and lente insulin (2%). Electrocardiograms (ECGs) were done in the previous two years on 267 patients (29%), among whom 38% had evidence of left ventricular hypertrophy and 16% of ischaemic heart disease. The level of blood pressure and blood glucose control was inadequate despite the provision of regular monitoring, surveillance and improved access to medication. It is perceived that poor socioeconomic conditions, lack of education, cultural beliefs and some other factors continue to militate against improved compliance and control. HOPE worldwide Jamaica is currently implementing programs to improve patient education, especially in compliance, to provide access to more effective medication with convenient once-daily dosage regimens, and to develop support groups among chronic disease patients in order to improve compliance and control.

Chronic Disease↗

[Stage I-III pulmonary sarcoidosis complicated by nephrogenic (vasopressin-resistant) form of diabetes insipidus].

Literature data and original experience of the authors with 6890 cases of respiratory sarcoidosis (stage I-III) suggest that diabetes ipsipidus in respiratory sarcoidosis (RS) can present as hypothalamic-hypophysial form (observed at the stage I-II by physicians since 1935) and a new form--nephrogenic (vasopressin-resistant) at stage II of pulmonary sarcoidosis. The latter form is little known. It was found that in stage III sarcoidosis patients who have severe fibrosis of the lungs and a long history of corticosteroid hormone treatment the nephrogenic form of the pathogenesis is caused by defects in calcium metabolism leading to nephrocalcinosis with low sensitivity of renal tubular receptors to ADH. Adiurecrine treatment is unefficient. It is recommended to use chlorpropamide which raises sensitivity of the tubules to ADH.

Diabetes Insipidus↗

[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

The development and progress of antidiabetic drugs (e.g., insulin preparations and hypoglycemic drugs) are retrospectively investigated in Japan. Their influences on the treatment of diabetes mellitus (DM) and its epidemiological aspects are also discussed. 1) Insulin preparations: Insulin was introduced for DM therapy in 1925, two or three years after its discovery in Canada. The preparations were raw extracts of bovine or porcine pancreas. These did not prevail widely in Japan because of the low incidence of DM before World Wan II. After the war, a shortage of mammalian materials compelled the use of fish pancreatic tissues such as bonito and/or tuna for insulin production. Insulin infection, so-called regular insulin, was first promoted in the 6th "Pharmacopoeia Japonica" (JP6) in 1951 and has been maintained to the present edition (JP14, 2001). Although depot-type insulin preparations were developed in the USA and Europe during the war, the introduction of those preparations to Japan was delayed until 1951, when Protamine zinc insulin appeared. Globin zinc insulin and Isophane insulin were introduced for clinical use in 1952 and 1955, respectively. These were also adopted for JP7 (1961). Biphasic-type insulin, which has a rapid onset and long duration of activity, appeared in 1965. Purified preparations from bovine or porcine sources have been available since 1980, which might be a strong reason for the decrease in insulin allergy. Insulin from animal origin has been supplied for almost 60 years since its discovery. Amino acid sequences of insulins from various species of animals were determined by the pioneering studies of Sanger and his associates. Human insulin, which differs from porcine insulin by only one amino acid, was produced by Novo researchers in 1982 using a semi-synthetic method. Then the Lilly group soon succeeded in obtaining human insulin by recombinant DNA technology in the same year. Both products were introduced to Japan in 1985, and the recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after-meal hyperglycemia of Type 2 diabetes. Epalrestat (Ono Yakuhin Co., 1992) is effective for diabetic neuropathy by reducing the formation of sorbitol. These anti-DM drugs were recently studied and developed in Japan. 4) The Japan Diabetes Society proposed a guideline on diagnostic criteria and treatment of diabetes mellitus (DM) in 1999 and revised it in 2002. DM is classified as insulin-dependent DM (Type l) and non-insulin dependent DM (Type 2). Type 1, juvenile onset DM, requires insulin therapy to prevent ketosis and to sustain life. Treatment of type 2, adult onset DM, is recommended as a step-by-step method, starting with dietary-exercise therapy, followed by oral hypoglycemic drugs and then insulin therapy. DM patients with complications should have a therapy devised to match their circumstances. 5) Epidemiological aspects: The mortality rate of DM compared to the time of drug appearance was traced from 1920 to 2000. The curve goes down slowly in the time frame of World War II, but rises from 1950 to 1970. The elevation could not be suppressed by the appearance of SUs, BGs or improved insulin preparations. The curve runs flat from 1980 to 1990, which might be related to the use of purified insulin or human insulin therapy. The mortality rate of DM indicates that death by hyperglycemic coma and other deaths resulting from complications are excluded. The survey of the principal cause of death by DM during the period of 1981-1990 indicates that the death rate due to hyperglycemic coma is only 1.7% of the total deaths caused by DM. The effect of drug therapy on all of the death resulting from DM is not detected. Hospital visitation and admission rates of the DM patients have been recorded since 1952 in Japan. This curve is rising continuously, and none of the antidiabetic drugs has been able to suppress it. These data show that the antidiabetic drugs relieve DM symptoms through their effective hypoglycemic actions, but that they cannot suppress the mortality rate of DM. It is possible that none of the drugs currently available can suppress the increasing tendency of DM patients.

Diabetes Mellitus↗

Analgesic, antiinflammatory and hypoglycemic effects of Sutherlandia frutescens R. BR. (variety Incana E. MEY.) [Fabaceae] shoot aqueous extract.

Previous studies on the pharmacology of South African medicinal plants in our laboratories and elsewhere have shown that some plants possess therapeutic attributes. One such ethnomedically useful plant is Sutherlandia frutescens R. BR. (family: Fabaceae). S. frutescens is widely used in South African traditional medicine for the management and/or control of a plethora of human ailments. In order to scientifically appraise some of the ethnomedical uses of S. frutescens, the present study was undertaken to investigate the analgesic, antiinflammatory and antidiabetic properties of the plant's shoot aqueous extract in experimental animal models. The analgesic effect of the herb's shoot extract was evaluated using the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and hypoglycemic effects of the plant's shoot aqueous extract were investigated in rats, using fresh egg albumin-induced pedal (paw) edema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (100 mg/kg) and chlorpropamide (250 mg/kg) were used, respectively, as reference drugs for comparison. S. frutescens shoot aqueous extract (50-800 mg/kg i.p.) produced significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (50-800 mg/kg p.o. or i.p.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (p < 0.05-0.001) hypoglycemia in rats. The various chemical constituents and secondary metabolites of the herb are speculated to account for the observed analgesic, antiinflammatory and hypoglycemic effects of the plant. The results of this experimental animal study suggest that S. frutescens shoot aqueous extract possesses analgesic, antiinflammatory, and hypoglycemic properties, and thus lend pharmacological credence to the suggested folkloric uses of the herb in the management and/or control of painful, arthritic and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.

Analgesics↗

Chronic disease control and compliance--the HOPE worldwide Jamaica experience.

HOPE worldwide Jamaica has provided mobile curative and preventative services to fourteen rural government clinics since 1994. The patient records of 1,091 chronic disease patients, aged >30 years between January and December 1999 were reviewed. They were all above 30 years of age with an average age of 64 years; 81% were female and 60% were hypertensive, 16% diabetic and 24% had both diabetes and hypertension. There were 2,390 visits for hypertension, with an average of 2 visits per patient. Thirty-four per cent of patients had BP of < or = 140/90 mmHg while 43% had BP <160/ 95 mmHg. Compliance was defined as daily consistency in taking prescribed medication. Forty-four per cent of hypertensives were non-compliant at the time of their visit. Anti-hypertensive treatment included thiazide diuretics (65%), reserpine (50%), ACE inhibitors (30%) and alpha-methyldopa (5%). There were 1,129 visits for diabetes, with an average of 2 visits per patient. Twenty-four per cent of diabetic patients were controlled to fasting blood glucose FBG levels of <6.7 mmol/l and 38% controlled to (FBG) levels <8 mmol/l. Thirty per cent of diabetics were non-compliant at the time of their visit. The most frequently used oral hypoglycaemic agents were metformin (78%), glyburide (43%) and chlorpropamide (30%). Fourteen per cent of diabetics were on treatment with insulin 70/30 (12%) and lente insulin (2%). Electrocardiograms (ECG) were done on 24% (n=267) of patients in the previous two years. Thirty-six per cent had evidence of left ventricular hypertrophy and 15% had evidence of ischaemic heart disease. The level of blood pressure and blood glucose control is inadequate, despitethe provision of regular monitoring, surveillance and improved access to pharmaceuticals. It is perceived that poor socioeconomic conditions, lack of education, cultural beliefs, in addition to other factors, continue to militate against improved compliance and control.

Adult↗

Characterization of sulfonylurea receptors and the action of potassium channel openers on cholinergic neurotransmission in guinea pig isolated small intestine.

Specific binding sites for [3H]glibenclamide, a potent ATP-sensitive K+ channel blocker, have been characterized in the isolated guinea pig longitudinal muscle-myenteric plexus preparation. The Scatchard plot of the saturation isotherm was curvilinear and revealed two binding sites, one of high affinity (Kd = 0.42 nM; maximum binding site = 156 fmol/mg of protein), the other of low affinity (Kd = 83 nM; maximum binding site = 3100 fmol/mg of protein). Displacement experiments in the presence of various sulfonylureas showed the same order of potency for the two binding sites (glibenclamide greater than gliquidone greater than glipizide glibornuride greater than chlorpropamide greater than tolbutamide). The K+ channel opener RP 49356 (but not diazoxide or cromakalim) displaced the [3H] glibenclamide with an IC50 of 4.8 microM. The effects of the K+ channel openers diazoxide, RP 49356, cromakalim and its two optical isomers BRL 38226 and BRL 38227 were also studied on the electrically induced contractions of isolated guinea pig small intestine. These compounds produce an inhibition of neurally evoked twitch height with pD2 values of 4.5 to 6.2 (BRL 38227 greater than cromakalim greater than RP 49356 greater than diazoxide, whereas BRL 38226 was practically ineffective). The effects of cromakalim and RP 49356 were antagonized competitively by glibenclamide (pA2 = 7.2) and other sulfonylureas, suggesting they act on ATP-sensitive K+ channels. Affinities of the sulfonylureas obtained from concentration-response curves to cromakalim on electrically induced contractions are better correlated with the IC50 value corresponding to the low affinity binding site than to the high affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters↗

Acute oral hypoglycemic ingestions.

We reviewed the poison center records of 48 consecutive reports of oral hypoglycemic exposure reported to the Rush Poison Control Center between January 1988 and December 1989. The average age of ingestion was 15.0 y (range 1 to 75 y). Twenty-three of the patients (48%) were male, while 25 (52%) were female. Twenty-nine patients ingested glyburide, 10 chlorpropamide, 6 glipizide, 2 tolbutamide, and 1 each for tolazamide and phenformin. One patient ingested both glyburide and tolbutamide. Sixteen cases (33%) involved coingestants. Accidental cause was the primary reason for ingestion in 33 cases (69%) with suicidal intent being mentioned in an additional 11 cases (23%). Thirteen patients (27%) were treated and released from a health care facility, while the same percentage of patients were admitted. There was no adverse effect in 24 patients (50%) while 9 patients (19%) had minor effects without residual disability. Only 2 patients (4%) experienced a major effect. No deaths were reported. We conclude that oral hypoglycemic ingestions generally have a successful outcome and there does not appear to be a significant difference whether a short/long acting agent or first/second-generation product was ingested.

Acute Disease↗

[Evaluation of a new immunoturbidimetry technique for measuring microalbuminuria].

Subclinical elevation of urinary albumin excretion is a good predictor of later clinical proteinuria. A simple, sensitive and rapid immunoturbidimetric method was developed to quantify urinary albumin excretion (URIN-PAK ImmunoMICRO LAB, Miles Italia Spa). In the presence of polyethylene glycol 6000, immunocomplex between human albumin and its specific antibody are rapidly formed (5-50 min, at room temperature). Absorbance reading are mode U 340 nm (Automatic Analyzer RA 1000, Technicon). The test is specific for albumin failing to cross react with other plasma proteins present in urine, as well as with glibenclamide, chlorpropamide, phenformin, hemoglobin, glucose, urea and thymol. The present method correlates with SCLAVO H-ALBUMIN RIA Kit (r = 0.9917). The test is suitable for clinical use.

Albuminuria↗

Endocrine crises. Hypoglycemia.

Hypoglycemia is defined as the occurrence of a wide variety of symptoms in association with a plasma glucose level of 40 mg/dL or less. The conditions associated with hypoglycemia in hospitalized patients include exogenous insulin administration, ethanol, drugs (especially chlorpropamide), renal insufficiency, liver disease, infections, total parenteral nutrition, treatment of hyperkalemia with insulin, extensive burns, neoplasia, pregnancy, and a wide variety of less common causes. Although clinical features are helpful in making a diagnosis, a significant proportion of the patients are either asymptomatic or present with symptoms of altered mental status. The diagnosis of hypoglycemia should be considered in all hospitalized patients presenting with adrenergic or neuroglycopenic symptoms and signs suggestive of hypoglycemia. A detailed history along with a physical examination and appropriate laboratory investigations usually identify the specific cause of the hypoglycemia. An episode of hypoglycemia, especially if severe, should be treated with prolonged intravenous infusion of glucose. Prompt recognition and management of hypoglycemia are necessary to prevent significant morbidity and mortality.

Aged↗

Pattern of pharmaceutical retailing of anti-diabetic products in Ibadan, Nigeria.

Twenty-four pharmacists in the city of Ibadan were surveyed through a self-administered structured questionnaire as to the extent of their involvement in the pharmaceutical retailing of antidiabetic products and their cost. Oral hypoglycemic agents especially, chlorpropamide (Diabenese) and glibenclamide (Daonil) were the most readily available drugs being obtainable from 21 (87.5%) pharmacies. Insulin was stocked regularly by only 14 (58.3%) of the pharmacists and insulin syringes and needles could be obtained from only 10 (41.6%) of the pharmacies. Among materials for urine testing, clinistix strip was the most readily available and fully one-third of the pharmacies did not stock any such material. The prices of all the products were disturbingly high and between 1983 and 1986 when retail prices were re-assessed, the cost of some materials had escalated by as much as 400%. Scarcity of antidiabetic products and their high cost pose serious challenges for those involved in the care of diabetic patients in Nigeria. Some suggestions have been made as to what steps both the government and the pharmaceutical industry can take in ensuring the availability of these life sustaining products for the increasingly large Nigerian diabetic population.

Community Pharmacy Services↗

The pattern of diabetes in a primary health care setting in Singapore.

This is a study of Diabetes mellitus and its treatment in a single doctor government primary health care clinic in Singapore. Data was collected on the entire 349 patients with diabetes attending this clinic over a three month period in 1987. We found there was an increasing number of diabetics with age and a substantial proportion was above 70 years of age. Only 7% had their diabetes treated with diet alone and 9.6% were treated with insulin. Most (61%) patients were on tolbutamide, with 17.6% on glibenclamide and 5.9% on chlorpropamide. Hypertension was found in 38% of the diabetic patients but was not associated with increase in age of the patient. The duration of diabetes, but not the age of the patient, was positively associated with the number of drugs taken by the patient (chi-squared, p less than 0.05).

Adolescent↗

Use of sulfonylurea agents in older diabetic patients.

The elderly patient with type II diabetes should be treated in much the same fashion as a younger person with the same disease, although emphasis needs to be placed on minimizing side effects, drug interactions, and hypoglycemia. Chlorpropamide should not be used in these patients, unless there is no other choice. The remaining agents--tolbutamide, acetohexamide, tolazamide, glyburide, and glipizide--should be started at low doses and gradually increased until optimal diabetic control is reached. The initial treatment goal is a FPG level of less than 180 mg/dl and a final goal is a 1- to 2-hour PPG concentration between 140 and 180 mg/dl. The glycosylated hemoglobin value should be no greater than 1.5% above the upper limit of normal, and should be lower, if possible. It must be kept in mind, however, that the closer diabetic patients are to achieving euglycemia, the more likely is hypoglycemia. Treatment goals therefore may have to be relaxed in someone at increased risk of hypoglycemia (e.g., patients with irregular eating habits or renal insufficiency) or when hypoglycemia may pose a greater hazard (e.g., patients with coronary artery or cerebral vascular disease). Patients on sulfonylurea agents should have blood glucose values measured once a month and glycosylated hemoglobin levels determined once every 3 months to alert the clinician to the possible need to adjust therapy. In this way, potential hypoglycemia can be avoided if blood glucose levels are drifting too low and chronic hyperglycemia can be identified and treated within a short period of time. When a patient's status changes--e.g., he is placed on new medication, becomes depressed and anorexic, or develops another medical problem--care must be taken to re-evaluate his diabetes management. Drugs such as sulfonamide antibiotics can potentiate the action of the sulfonylureas and cause hypoglycemia, renal insufficiency may necessitate changing the type of sulfonylurea agent or decreasing the dose, and malnutrition may obviate any need for therapy with an oral hypoglycemic agent. If these guidelines are kept in mind, the older diabetic patient can be managed on a sulfonylurea agent in conjunction with the appropriate diet. Should these measures prove to be ineffective, then insulin therapy should be instituted. Controlling chronic hyperglycemia will help improve the quality of life for patients with diabetes and decrease the probability of developing some of the devastating complications associated with this disease.

Aged↗