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PubMed2001

Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies.

A group of international experts prepared two lists of drugs with their serum/plasma and urine concentrations, which should be used when evaluating the performance of a new laboratory method. The two lists were verified by running in vitro interference studies in three European laboratories on Hitachi instruments. The study identified the following new interferants: acid phosphatase in serum by ibuprofen and theophylline; non-prostatic acid phosphatase in serum by cefoxitin and doxycycline; creatine kinase MB in serum by doxycycline; total bilirubin in serum (Jendrassik-Grof method) by rifampicin and intralipid; total bilirubin in serum (DPD method) by intralipid; creatinine in serum (Jaffe method) by cefoxitin; fructosamine in serum by levodopa and methyldopa; uric acid in serum by levodopa, methyldopa and tetracycline; carbamazepine in serum by doxycycline, levodopa, methyldopa and metronidazole; digitoxin in serum by rifampicin; phenytoin in serum by doxycycline, ibuprofen, metronidazole and theophylline; theophylline in serum by acetaminophen, cefoxitin, doxycycline, levodopa, phenylbutazone and rifampicin; tobramycin in serum by cefoxitin, doxycycline, levodopa, rifampicin and phenylbutazone; valproic acid in serum by phenylbutazone; C3 in serum by intralipid; C4 in serum by doxycycline; rheumatoid factor in serum by ibuprofen and metronidazole; pancreatic amylase and total amylase in urine by acetylcysteine, ascorbic acid, cefoxitin, gentamicin, levodopa, methyldopa and ofloxacin; magnesium in urine by acetylcysteine, gentamicin and methyldopa; beta2-microglobulin in urine by ascorbic acid; total protein in urine by ascorbic acid, Ca-dobesilate and phenylbutazone. Interference in acid phosphatase, creatine kinase MB and bilirubin methods was observed at very low analyte concentrations, and therefore it may not be evident at higher concentrations. The study confirmed the usefulness of the recommendation.

Blood Chemical Analysis↗
PubMed1995

Protein glycation inhibitors from thyme (Thymus vulgaris).

Nonenzymatic glycation of bovine serum albumin (BSA) was inhibited in vitro by some extracts of 34 kinds of spices. The methanol extract of thyme (Thymus vulgaris) had the most potent inhibitory activity among them. Chromatographic purification yielded four flavonoids, quercetin (1), eriodictyol (2), 5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone (3), and cirsilineol (4). These known flavonoids suppressed the levels of advanced glycation end products (AGEs) and fructosamines, shown by the measurement of specific fluorescent groups and the reduction of nitroblue tetrazolium (NBT), respectively. The inhibitory activities were compared with those of other structure-related flavonoids and aminoguanidine.

Flavonoids↗
PubMed2004

Diabetes mellitus non-glucose monitoring: point-of-care testing.

OBJECTIVE: To review and evaluate reimbursable point-of-care testing devices yielding immediate results, other than glucometers, that are available to evaluate and monitor diabetes and its complications and to describe how pharmacists may use these devices. DATA SOURCES: A MEDLINE search (1966-March 2003) was performed using the following search terms: point-of-care systems, clinical diabetes monitoring, decision support systems, glycosylated hemoglobin, and microalbumin. Pertinent company and product Web sites and customer service departments were accessed for information about point-of-care devices and supplies. STUDY SELECTION AND DATA EXTRACTION: All descriptive, evaluative, and comparative articles and product information were reviewed, and relevant information was included. DATA SYNTHESIS: Diabetes mellitus is a complex, chronic metabolic disease that is a challenging management problem and requires routine monitoring for disease control and screening for complications. Point-of-care tests are available to monitor hemoglobin A(1c), glucose, fructosamine, ketones, lipid profiles, urinary microalbumin concentrations, and alanine aminotransferase concentrations. Many of these tests are Clinical Laboratory Improvement Amendments (CLIA)-waived and, therefore, practical for pharmacists to use in a variety of settings. Tests for measuring sensation are also discussed. Pharmacists should consider each of these tests in the establishment of a comprehensive diabetes care service. CONCLUSIONS: The availability of many new point-of-care testing methods creates new opportunities for pharmacists to monitor drug therapy and screen for complications in patients with diabetes. Reimbursement is possible since many of these tests are CLIA-waived.

Albuminuria↗
PubMed2005

Effect of L-carnitine on acetyl-CoA content and activity of blood platelets in healthy and diabetic persons.

BACKGROUND: Excessive blood platelet activity contributes to vascular complications in diabetic persons. Increased acetyl-CoA in platelets from diabetic persons has been suggested to be a cause of this hyperactivity. We therefore investigated whether L-carnitine, which up-regulates metabolism of acetyl-CoA in muscles and brain, may affect platelet function in healthy and diabetic individuals. METHODS: We obtained platelets from healthy and diabetic persons and measured acetyl-CoA concentrations, malonyl dialdehyde (MDA) synthesis, and platelet aggregation in the absence and presence of L-carnitine. Activities of selected enzymes involved in glucose and acetyl-CoA metabolism were also assessed. RESULTS: Fasting glucose, fructosamine, and hemoglobin A1c were present in significantly higher amounts in the blood of diabetic patients than in healthy individuals. Activities of carnitine acetyltransferase, glucose-6-phosphate dehydrogenase, oxoglutarate dehydrogenase, and fatty acid synthase were 17%-62% higher in platelets from diabetic patients. Mitochondrial acetyl-CoA was increased by 98% in platelets from diabetic patients, MDA synthesis was increased by 73%, and platelet aggregation by 60%. L-Carnitine had no or only a slight effect on these indices in platelets from healthy individuals, but in platelets from diabetic patients, L-carnitine caused a 99% increase in acetyl-CoA in the cytoplasmic compartment along with increases in MDA synthesis and platelet aggregation. CONCLUSIONS: Excessive platelet activity in persons with diabetes may result from increased acetyl-CoA, which apparently increases synthesis of lipid activators of platelet function. L-Carnitine may aggravate platelet hyperactivity in diabetic persons by increasing the provision of surplus acetyl-CoA to the cytoplasmic compartment.

Acetyl Coenzyme A↗
PubMed2006

Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus.

The aim of this study was to determine the effect of chromium (Cr)- enriched yeast on blood glucose and insulin variables, blood lipids, and blood markers of oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0 yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass index: 34.33 kg/m2) were supplemented with 400 microg Cr/d as Cr-enriched yeast (n = 19) or placebo (n = 17) for 12 wk in a randomized, double-blind study. The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group. The Cr group showed a significantly greater increase in serum Cr compared to the placebo group (p < 0.05). Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo (p < 0.01). Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk, but decreased significantly in the placebo group (p < 0.05, p < 0.01, respectively). Serum HbA1c and glycated protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA1c tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum insulin decreased in both groups, with a greater tendency in the Cr group (-16.5% vs -9.5%). These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress.

Aged↗
PubMed1991

[HLA-antigens in thyrotoxic patients with overt diabetes mellitus].

The incidence of thyrotoxicosis accompanied by overt diabetes has been reported to be 2 to 3%. Several workers have suggested the possible role of immunological and inherited factors in the occurrence of thyrotoxic patients with overt diabetes. We investigated, therefore, the clinical characteristics, backgrounds, and HLA antigens in thyrotoxic patients with overt diabetes. In nine thyrotoxic patients with overt diabetes (group DM) (3 men and 6 females, average age of 45.8 +/- 2.9 yr), mean levels of free-triiodothyronine (FT3) and free thyroxine (FT4) were 8.2 +/- 0.8 pg/ml and 4.9 +/- 0.4 ng/dl, respectively. Although these levels were extremely high, they were significantly lower than those levels in forty thyrotoxic patients without overt diabetes (group ND) (8 men and 32 females, average age 35.1 +/- 4.5 yr). Mean levels of both thyrotrophin receptor-antibody (TR-Ab) and thyroid simulating antibody (TS-Ab) in group DM were relatively lower than those in group ND. Mean titers of both antithyroid antibody (TGHA) and antimicrosomal antibody (MCHA) in group DM were also relatively lower than those in group ND, respectively. Regarding the clinical features in thyrotoxic patients with overt diabetes, mean duration of diabetes mellitus was 4.1 +/- 2.5 years with mean levels of fasting plasma glucose (FPG), HbA1c, and serum fructosamine 208.1 +/- 34.0 mg/dl, 10.6 +/- 0.6%, and 3.9 +/- 0.9 mmol/L, respectively. Seven patients in group DM frequently had ketosis or ketoacidosis in their histories, and they had been treated with insulin injection. However, the diabetic complications in group DM were moderate or severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Can we use plasma fibronectin levels as a marker for early diabetic nephropathy.

Although increased plasma fibronectin (PF) levels have been found in diabetic patients with microalbuminuria, there is still controversy about its clinical implication for detecting early diabetic nephropathy. To evaluate the PF concentration as a possible marker for early diabetic nephropathy, three groups of sex-and age-matched patients were studied I) 22 insulin dependent diabetic (IDDM) patients with microalbuminuria (mean age +/- SEM: 23.3 +/- 3.6 years, mean urinary albumin excretion rate (AER) +/- SEM: 47.1 +/- 39.5 micrograms/min); II) 17 IDDM patients with normoalbuminuria (mean age: 23.4 +/- 4.4 years, mean AER: 7.8 +/- 2.1 micrograms/min) and III) 20 healthy control subjects (mean age: 22.6 +/- 4.1 years, mean AER: 6.7 +/- 2.1 micrograms/min). PF and urinary excretion of albumin were measured by an immunoturbidimetric method using commercially available kits (Boehringer Mannheim GMBH FRG, and Miles Lab., UK). The mean PF was significantly higher in the group with microalbuminuria (406.5 +/- 122.9 micrograms/ml) than in the group with normoalbuminuria (295.6 +/- 96.9 micrograms/ml, P < 0.01) or in the control group (299.54 +/- 105.5 micrograms/ml, P < 0.01). A weak positive correlation was found between PF and urinary albumin values (r = 0.35, P < 0.05). There were no significant correlations between PF and the other variables such as age, duration of diabetes, body mass index, arterial blood pressure, fasting blood glucose, fructosamine and HbA1 in the diabetic patients or in the control group. Our results suggest that the PF concentration could be a weak marker for early diabetic nephropathy. We cannot therefore use PF instead of microalbuminuria because there is only a weak correlation between PF and microalbuminuria.

Adult↗
PubMed1991

Microalbuminuria in diabetic patients: relationship to lipid, glyco-metabolic, coagulation and fibrinolysis parameters.

One hundred and sixteen insulin treated diabetic patients were evaluated for the relationship between the presence of microalbuminuria and several lipid, glyco-metabolic, coagulation and fibrinolysis factors. A significant correlation existed only between microalbuminuria and HbA1c (r = 0.23, p = 0.008) and D-dimer (r = 0.28, p = 0.002). After the subdivision of the patients in a group without (n = 85) and a group with microalbuminuria (n = 31) significant differences were found between these two groups for the HDL-cholesterol content (p less than 0.05), the HbA1c level (p less than 0.01) and for the D-dimer concentration (p less than 0.01). Comparison of the patient groups without and with microalbuminuria separately with a healthy volunteers group without albuminuria resulted in significant differences for HDL-cholesterol, triacylglycerols, HbA1c, fructosamine, fibrin monomer and D-dimer, whereas fibrinogen also was significantly different between the diabetic group without microalbuminuria and the healthy volunteers group. Several factors predisposing for atherosclerosis (decrease of HDL-cholesterol, increase of triacylglycerols, coagulation activation with relatively insufficient fibrinolysis) were noticed in both diabetic groups without or with microalbuminuria, but more pronounced in the latter group. The appliance of a Receiver Operating Characteristic (ROC) curve for HbA1c against microalbuminuria (cut-off level 20 micrograms/min) reconfirmed the value of adequate glycaemic control in diabetics for the prevention of microalbuminuria. In conclusion the results of this study show a significantly poorer glycaemic control in insulin treated diabetics with microalbuminuria than in those without microalbuminuria. The presence of lower HDL-cholesterol, higher triacylglycerols and the elevation of fibrin monomers and D-dimers is more pronounced in the microalbuminuria group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2000

Influence of in vivo hemoglobin carbamylation on HbA1c measurements by various methods.

Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with HbA1c assays, but few studies compared directly both parameters. We measured carbamylated hemoglobin by HPLC in 45 non-diabetic uremic patients (16 with acute and two with chronic renal failure, 27 with transplant recipients) as 57.8 +/- 22.3 microg carbamylvaline/g Hb (mean +/- standard deviation) vs. 31.6 +/- 5.1 in 15 controls (+83%, p < 0.001). In these samples, HbA1c was evaluated by three ion-exchange HPLC methods, 1: Diamat (BioRad), 2: A1c2.2 (Tosoh) and 3: HA8140 (Menarini), and one immunoassay method (Tinaquant II Roche). Whichever the method, mean HbA1c values obtained increased in patients with high (> 60 microg carbamylvaline/g Hb) vs. low (< 45) carbamylated hemoglobin values (+0.08 to 0.25% of total Hb), but differences were not significant. Minor peaks on the chromatograms were however increased in parallel to carbamylated hemoglobin. HbA1c values over 6% were found in 4, 1, 2 and 0 samples, with HPLC 1, 2, 3 and immunoassay, respectively. Fructosamine values were not significantly altered. Our results show that Hb adducts, whether due to carbamylation or to other chemical reactions, interfere to a variable extent with different HbA1c assay methods, and confirm that HbA1c values should be interpreted with caution in uremic patients.

Adolescent↗
PubMed2003

Platelet function and acetyl-coenzyme A metabolism in type 1 diabetes mellitus.

Blood platelets take up glucose through insulin-independent GLUT-3 transporter. It is, however, unclear how diabetes affects further steps of glucose and glucose-derived acetyl-coenzyme A (CoA) metabolism in platelets. There is no evidence to explain whether these changes are linked to the disease-induced disturbances in platelet function. We found that activities of some key enzymes of glucose and acetyl-CoA metabolism in platelets were elevated in diabetes. Activities of hexokinase, pyruvate dehydrogenase and ATP-citrate lyase in diabetic platelets were found to be increased by 53, 56 and 88%, respectively. Accordingly, diabetes brought about 86% increase of platelet acetyl-CoA and activation of malonyl dialdehyde synthesis as well as spontaneous and thrombin-induced platelet aggregation by about 56, 50 and 15%, respectively. Significant correlations have been observed between some parameters of acetyl-CoA metabolism, platelet function and serum fructosamine in diabetic patients but not in healthy individuals. Our findings indicate that increased platelet activity in diabetic subjects may, at least in part, result from chronic hyperglycaemia-induced changes in acetyl-CoA metabolism, yielding an increase in its concentration in platelets.

Acetyl Coenzyme A↗
PubMed1997

Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus.

UNLABELLED: In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine the metabolic and hormonal responses to an unchanged insulin therapy with the addition of a subcutaneous administration of recombinant human IGF-I (rhIGF-I) during (a) a short-term (2 weeks) period with rhIGF-I given twice a day in a high dose (80 micrograms/kg body weight) in four patients with extreme insulin-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin receptor mRNA, whereas the remaining two patients were suspected to have defects at receptor and/or post-receptor sites. In the short-term study period, plasma glucose levels decreased more than 35% in response to rhIGF-I in all but one patient which was paralleled by reduced levels of serum insulin (25-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum insulin and C-peptide levels were decreased by 40-55% after 6 weeks in the two siblings with known insulin receptor mutations. After 10 weeks of treatment fasting plasma glucose levels were still decreased whereas fasting serum insulin and C-peptide levels were increased almost to pretreatment values. IN CONCLUSION: 2 weeks of high-dose rhIGF-I therapy in insulin-treated patients with severe insulin resistance has a marked lowering effect on fasting plasma glucose and serum insulin levels whereas the metabolic and glycaemic effects of 10 weeks of treatment with low-dose rhIGF-I may be modest and transient.

Adolescent↗
PubMed1991

Protein glycation: its role in the changes induced by diabetes in the properties of the serum insulin-like growth factor-I binding proteins.

The purpose of this work was to study the effect of diabetes on 125I-labelled insulin-like growth factor (IGF) binding to specific serum binding proteins (IGFBPs) and the possible role of protein glycation in such an effect. Accordingly, ligand blotting and fructosamine assays were performed in serum samples from diabetic and non-diabetic eSS rats as well as in samples of normal rat serum previously incubated with different concentrations of glucose. IGFBPs with molecular weights of 24, 30 and 40 kDa were identified in samples from diabetic and non-diabetic rats. 125I-Labelled IGF-I binding to each of these fractions increased significantly in the serum of diabetic rats. IGF-I binding to IGFBP-40 increased significantly as a function of the degree of glycation of serum proteins. Conversely, the increased binding of IGFBP-24 and IGFBP-30 was related only to the glucose concentration attained at 120 min during the oral glucose tolerance test. Glycation of proteins of normal serum and the binding of labelled IGF-I increased as a function of glucose concentration in the incubation media. In these in-vitro glycated normal sera, only the binding to IGFBP-40 increased significantly; this increase was closely related to the amount of protein glycation. No clear and reproducible changes occurred with the binding of 125I-labelled IGF-I to IGFBP-24 and IGFBP-30 fractions. These results confirm the increase in the binding capacity of IGFBPs reported in diabetic animals. They also show that the increase in IGF-I binding to each IGFBP fraction is regulated by a different mechanism; whereas protein glycation induces changes in IGFBP-40, this mechanism does not affect the binding properties of the other two IGFBPs. The increased binding of IGFBP might affect the availability of free IGF-I, and the consequent alterations in IGF-I-dependent metabolic processes could explain the role of this growth factor in the pathogenesis of chronic complications of diabetes.

Animals↗
PubMed2001

Glucose-modified proteins modulate essential functions and apoptosis of polymorphonuclear leukocytes.

Any modulation of the activity of polymorphonuclear leukocytes (PMNL) is a potential cause of the altered immune response in uremia. Because the level of glycation products is elevated in uremic sera and peritoneal effluents, the effect of glycated proteins on essential functions and on apoptosis of PMNL was investigated. Proteins from sera of healthy donors were incubated with and without glucose. The extent of early glycation was monitored by boronate chromatography and the fructosamine assay. The formation of late glycation products was assessed by fluorescence spectroscopy and Western blotting that used a specific antibody for imidazolone, a late glycation product. With the addition of aminoguanidine, a compound that inhibits the formation of late but not of early glycation products, protein samples with early glycation only were obtained. Glucose-modified proteins increased chemotaxis and activation of the 2-deoxy-D-glucose uptake of PMNL obtained from healthy donors, compared with those of unmodified proteins. PMNL apoptosis, assessed by morphologic changes, by detecting DNA strand breaks, and by measurement of the caspase 3 activity, was increased in the presence of glucose-modified serum proteins. It was found that the formation of late glycation products is necessary for the effect on PMNL chemotaxis. In contrast, early glycation of proteins is responsible for the increase of glucose uptake and apoptosis. It was concluded that the accumulation of glycated proteins in uremic sera and peritoneal fluid may contribute to the diminished immune function observed in uremia, by modulation of essential PMNL functions and acceleration of PMNL apoptosis.

Apoptosis↗
PubMed2005

Pramlintide acetate.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of pramlintide are reviewed. SUMMARY: Pramlintide, a synthetic analogue of the human hormone amylin, is the first of a new class of amylinomimetic compounds. It was approved in March 2005 as a subcutaneous injection for the adjunctive treatment of patients who have type 1 or 2 diabetes mellitus and have failed to achieve glycemic control despite optimal therapy with insulin. Pramlintide complements the effects of insulin in postprandial glucose regulation by decreasing glucagon secretion. Pramlintide exhibits linear pharmacokinetics, and peak serum levels are reached within 30 minutes of administration. The drug is predominantly renally eliminated, with a mean elimination half-life of 30-50 minutes. Clinical trials have shown that pramlintide suppresses postmeal glucagon secretion, slows gastric emptying, reduces postprandial glucose levels, and improves glycemic control while managing weight loss. Pramlintide has also been shown to decrease hemoglobin A(1c), serum fructosamine, and total cholesterol levels. Pramlintide has been associated with an increased risk of insulin-induced severe hypoglycemia; other adverse events include nausea, anorexia, fatigue, and vomiting. The dosage varies with the type of diabetes. Because of the cost associated with the complications of uncontrolled diabetes, pramlintide may have a beneficial effect on total costs associated with this chronic disease. CONCLUSION: Pramlintide in combination with insulin is a potential therapeutic option for improving glycemic control in patients with diabetes, but the increased risk of hypoglycemia must be aggressively monitored.

Amyloid↗
PubMed1991

The management of diabetes mellitus in older individuals.

Nearly 50% of individuals with type II diabetes mellitus are over the age of 65 years. There are numerous reasons to maintain blood glucose levels below 11.1 nmol/L (200 mg/dl) in older persons, and there are a number of changes often seen with advancing age that persons, and there are a number of changes often seen with advancing age that may interfere with the management of diabetes mellitus, e.g. hypodipsia, anorexia, visual disturbance, altered renal and hepatic function, depression, impaired basoreceptor response and multiple medications. Hyperglycaemia appears to produce cognitive impairment which may lead to poor compliance. It is often difficult to manipulate diet in older people, and in fact dietary changes can lead to severe protein energy malnutrition. High maximum voluntary oxygen intake has been correlated with increased glucose disposal, but there is little evidence that physical exercise can improve diabetic control in the elderly. Oral sulphonylurea hypoglycaemic agents are extremely useful in the treatment of diabetes in these patients, but it should be remembered that they are more liable to develop hypoglycaemia than are younger diabetics. The role of metformin in the management of older diabetic patients is poorly studied. Many older persons can cope well with insulin therapy, but those with visual disturbances often make errors when drawing up insulin and require special attention. Combination therapy of insulin with oral hypoglycaemic agents is not recommended in this group of patients, and serum fructosamine is preferred to glycated haemoglobin to monitor control. Successful management of elderly diabetic patients thus requires an interdisciplinary team approach.

Aging↗
PubMed1992

Swiss hypertension treatment programme with verapamil and/or enalapril in diabetic patients.

The purpose of the present study was to assess the efficacy and tolerability of diuretic-free antihypertensive therapy with a calcium antagonist and/or an angiotensin converting enzyme (ACE) inhibitor in patients with diabetes mellitus. 54 hypertensive [blood pressure (BP) above 140/90mm Hg] patients with diabetes mellitus type 1 (n = 7) or 2 (n = 47) and normal serum creatinine levels (mean 82 +/- 6 mumol/L) received either verapamil or enalapril after a 2-week washout and a 4-week placebo phase. If BP remained elevated, both agents were combined. Verapamil or enalapril alone normalised diastolic BP (to less than 90mm Hg) in 36 patients; verapamil decreased BP from 159/98 to 147/87mm Hg (n = 19, p < 0.001) and enalapril decreased BP from 166/99 to 146/88mm Hg (n = 17, p < 0.001). In 18 patients who remained hypertensive after 10 weeks of monotherapy, a combination of both drugs decreased BP from 169/104 to 151/90mm Hg (p < 0.001). Overall, 87% of patients achieved a target BP response at 30 weeks. Urinary albumin as related to creatinine excretion (UAE; micrograms albumin:mg creatinine) was on average not significantly changed after verapamil or enalapril treatment, alone or combined. Nevertheless, in patients with initial microalbuminuria, UAE decreased (p < 0.05) during enalapril treatment. Serum potassium, total lipids, high density lipoprotein cholesterol, low density lipoprotein cholesterol, glycosylated haemoglobin, serum C peptide and fructosamine levels were not significantly modified by treatment. Subjective tolerability of the drugs was also generally good. Thus, in hypertensive patients with diabetes, a diuretic-free therapy based on the calcium antagonist verapamil or the ACE inhibitor enalapril, alone or combined, can effectively decrease BP without adversely affecting carbohydrate and lipid metabolism.

Adolescent↗
PubMed2005

[Relationship between low glomerular filtration rate, hypertension, and microalbuminuria in type 1 diabetes mellitus].

AIM: To investigate the influence of low glomerular filtration rate, as well as of systolic and diastolic hypertension, on microalbuminuria in patients with type 1 diabetes mellitus. METHODS: Twenty seven patients with type 1 diabetes mellitus (18 males, 9 females) were studied. All of the patients were below 50 years of age. In 93% of the cases, the duration of diabetes was less than 15 years. GFR was determined, after intravenous injection in the lying position, by using a 99m-Tc-DTPA, while microalbuminuria was calculated for the 24-hour urine using the nephelometric immunoassay (30-300 mg/24 h). The patients were divided into 3 groups according to the value of GFR. The values ranged from 90 to 125 ml/min/1.73 m2 were considered normal (in 63% of the patients in group 1), those above that range were considered as hyperfiltration (in 22.2% of the patients in group 2), while those below that range were considered as hypofiltration (in 13.8% of the patient in group 3). RESULTS: Data analyzed with the one-way ANOVA, indicated a significant statistical difference between the 3 groups in the duration of diabetes (p < 0.05), micro-albuminuria (p < 0.01), systolic BP (p < 0.01), diastolic BP (p < 0.05), fructosamine (p = 0.50), urea (p < 0.05), creatinine (p = 0.05), and uric acid (p < 0.05). Microalbuminuria correlated with the age of patients (p <0.05) (Spearman's rho), diabetes mellitus duration (p < 0.01), systolic BP (p < 0.05), diastolic BP (p < 0.05), LDL-cholesterol (p < 0.05). There was no statistically significant correlation between GFR and the other parameters. Hypertension, microalbuminuria, and the duration of diabetes correlated positively with the reduction of GFR, revealing the most frequent reduction of GFR in the patients with more than 15-year duration of diabetes. CONCLUSIONS: Hypertension and low GFR were associated with microalbuminuria in type 1 diabetes, while the duration of diabetes was shown to be the independent risk factor for the development of microalbuminuria.

Adult↗
PubMed2006

Continuous glucose monitoring-guided insulin adjustment in children and adolescents on near-physiological insulin regimens: a randomized controlled trial.

OBJECTIVE: This randomized controlled trial assesses the effect on glycemic control of continuous glucose monitoring system (CGMS)-guided insulin therapy adjustment in young people with type 1 diabetes on intensive diabetes treatment regimens with continuous subcutaneous insulin infusion (CSII) or glargine. RESEARCH DESIGN AND METHODS: Pediatric subjects were recruited if they had an HbA(1c) (A1C) <10% and had been on CSII or glargine for at least 3 months. Thirty-six subjects were randomized to insulin adjustment on the basis of 72 h of CGMS every 3 weeks or intermittent self-monitoring of blood glucose (SMBG) for 3 months. A1C and fructosamine were measured at baseline and 6 and 12 weeks. Follow-up A1C was measured at 6 months. Mean baseline A1C was 8.2% (n = 19) in the CGMS group and 7.9% (n = 17) in the control group. RESULTS: There was a significant improvement in A1C from baseline values in both groups, but there was no difference in the degree of improvement in A1C at 12 weeks between the CGMS (-0.4% [95% CI -0.7 to -0.1]) and the control group (-0.4% [-0.8 to 0.2]). In the CGMS group, improved A1C was at the cost of increased duration of hypoglycemia. CONCLUSIONS: CGMS is no more useful than intermittent fingerstick SMBG and frequent review in improving diabetes control in reasonably well-controlled patients on near-physiological insulin regimens when used in an outpatient clinic setting.

Adolescent↗