Cyndrome

Archive for June, 2010

A pilot study has shown that absorption of oral insulin is possible in fasting conditions and that it has a fast onset and short duration of action in patients with Type 2 diabetes.

Oral insulin exhibited early, enhanced pharmacokinetic and pharmacodynamic responses compared with subcutaneous injection of regular human insulin, report Christoph Kapitza (Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany) and colleagues.

Gastrointestinal absorption of oral insulin is hampered by factors such as enzymatic degradation and lack of permeation through epithelial cells, say the researchers.

They tested the value of combining human insulin with the novel drug-carrier molecule monosodium N-(4-chlorosalicyloyl)-4-aminobutyrate (4-CNAB) to facilitate gastrointestinal absorption in a single-center, open-label randomized study.

The proof-of-concept research included 10 men who had been diagnosed with Type 2 diabetes for over a year who were not treated with insulin therapy.

Participants underwent an overnight fast before receiving two capsules that each contained 150 U of oral insulin plus 200 mg 4-CNAB, or a subcutaneous injection for 15 U of regular human insulin on two separate occasions separated by up to 20 days.

Maximum plasma insulin concentration was significantly greater with oral administration than subcutaneous injection, at a mean of 93 versus 33 µU/ml. Oral insulin also had a faster onset of action, with a corresponding area under the curve for glucose infusion rates in the first hour of 173 versus 27 mg/kg.

Mean insulin concentration and glucose infusion rate returned to baseline within 3 hours of oral insulin administration. A mean of just 7%was absorbed in the 2 hours following oral insulin administration.

Reporting in the journal Diabetes Care, the team suggests: “The fast pharmacokinetic and metabolic time-profiles of [oral insulin] observed in this study may be advantageous in patients with Type 2 diabetes by restoring normal first phase insulin secretion and potentially leading to an improvement in glycemic control.”

Assessing the age and fasting blood glucose (FBG) of cardiac patients can help to reduce the need for oral glucose tolerance tests (OGTTs) to detect undiagnosed Type 2 diabetes, researchers suggest.

Guidelines recommend screening all patients with cardiovascular disease with an OGTT, but prior research suggests this may only occur in half of all patients, say the German investigators.

“The main handicap why an OGTT is not performed in daily routine might be its intensiveness in time, personnel and costs,” they suggest in the International Journal of Cardiology.

In a search for clinical markers that could be used to identify high-risk patients who would benefit most from OGTT screening, they studied the predictive value of easily available clinical markers for undiagnosed Type 2 diabetes.

OGTTs were performed in all 1215 patients without known Type 2 diabetes who presented at a heart center with known or suspected coronary artery disease for elective coronary angiography from January to October 2007.

Results showed that 31.4% of the patients had normal glucose tolerance, 50.7% had impaired fasting glucose or impaired glucose tolerance, and 17.9% were newly diagnosed with Type 2 diabetes. Therefore, 998 OGTTs did not result in the new diagnosis of undiagnosed diabetes, the team calculates.

FBG of at least 90 mg/dl and age of at least 55 years predicted undiagnosed diabetes. At these cut-off points, Type 2 diabetes could be diagnosed with a sensitivity of 81.1%, a specificity of 63.4%, and a positive predictive value of 32.5%.

“Thus, the number of subjects needed to be screened could be reduced from 1215 to 541, and costs and other resources of more than 55% of OGTTs be saved,” report Mark Lankisch (University of Witten, Dortmund) and colleagues.

They conclude: “The implementation of simple and rapid available measures as FBG and age is a helpful tool to reduce the number of OGTTs needed for the detection of so far undiagnosed Type 2 diabetes mellitis so that national and international guidelines can be followed more easily and unknown Type 2 diabetes mellitis can be detected more effectively.”

A study is underway in Europe to assess the feasibility and impact of the “chronic care model” as a framework for managing patients with Type 2 diabetes.

The trial, known as “CARAT” (The Chronic CARe for diAbeTes study), was launched in Switzerland in February 2010 and is employing a cluster randomized design. The trial design and rationale are published in the open-access journalCardiovascular Diabetology.

“Chronic conditions and multimorbidity represent the major challenge for the health care systems in the industrialized world,” explain Anja Frei (University of Zurich) and fellow CARAT investigators.

“The chronic care model provides a proactive, patient-centred, evidence-based approach to face this challenge.”

Recent studies in a range of chronic diseases have demonstrated that treatment strategies incorporating elements of the chronic care model lead to improved outcomes for both patients and healthcare systems.

To date, however, most of these studies have been performed in the USA, which has a very different healthcare system to that of Europe.

The CARAT trial aims to address this gap by adapting the chronic care model approach to the Swiss healthcare system. A total of 28 general practitioners (GPs) in Switzerland will be randomly assigned to either intervention or control; each GP will enrol 12 patients with Type 2 diabetes.

The intervention will entail the GP and practice nurse working as a team to deliver comprehensive diabetes care tailored to the needs of the individual patient; the control group will receive care as usual.

The primary endpoint is the change in glycated hemoglobin between baseline and 1 year. Secondary endpoints include control of of blood pressure, glycated hemoglobin, and low-density lipoprotein cholesterol; quality-of-life; and quality indicators of diabetes care.

“This study challenges the hypothesis that the chronic care model can be easily implemented by a practice-nurse-focused approach,” write Frei et al.

“If our results will confirm this hypothesis, the suggestion arises whether this approach should be implemented in other chronic diseases and multimorbid patients and how to redesign care in Switzerland.”

Men with diabetes have a significantly reduced risk for prostate cancer compared with their nondiabetic peers, report researchers.

The team notes that there was a borderline significant trend for a greater inverse association with well versus poorly differentiated cancers.

“Observational studies suggest that diabetes is associated with a decreased risk of prostate cancer, but few are population based or have investigated associations with cancer stage or duration of diabetes,” say Richard Martin (University of Bristol, UK) and colleagues.

They report the results of a nested case-control study of 1291 men with histologically confirmed prostate cancer, aged 50–69 years, and 6479 age- and general practice-matched controls from the ProtecT (Prostate testing for cancer and Treatment) study based in the UK.

They found that the prevalence of diabetes was significantly lower in men with prostate cancer than controls, at 6.9% versus 8.6%. Presence of diabetes reduced the relative risk for prostate cancer by 22%.

There was weak evidence for the inverse association being greater for well versus poorly differentiated cancers, which was still borderline significant after adjustment for family history of prostate cancer.

Adjustment for body mass index weakened the inverse association slightly, but it was still statistically significant. There was no evidence for a greater reduction in prostate cancer risk with longer time since diabetes diagnosis.

The authors suggest that low insulin levels in men with diabetes “may suppress prostate carcinogenesis directly or by reducing levels or activity of insulin growth factor-I, a putative risk factor for prostate cancer.”

They conclude in the International Journal of Cancer: “These data add to the evidence of the association of diabetes with prostate cancer in the prostate specific antigen era.”

Women with Type 2 diabetes have significantly increased risk for genital and digestive cancers compared with their nondiabetic peers, show study results.

However, men and women with diabetes have significantly reduced risks for prostate cancer and skin cancer, respectively.

“Type 2 diabetes mellitus has been associated with an increased risk of a variety of cancers in observational studies, but few have reported the relationship between diabetes and cancer risk in men and women separately,” write Gabriel Chodick (Tel Aviv University, Israel) and team.

They therefore followed up 16,721 Type 2 diabetics and 83,874 nondiabetics (52.6% male) for 8 years for incidence of cancers by gender.

In total, 1639 and 7945 cases of incident cancer were reported in diabetic and nondiabetic participants, respectively, over the study period. Women with diabetes had a significant 23% increase in risk for total cancer compared with nondiabetic women, but no such increase in total cancer risk was seen in diabetic versus nondiabetic men.

Regarding different cancer subtypes, women with diabetes had a significant 96% and 41% increase in relative risk for cancers of the genital and digestive organs, respectively, compared with nondiabetic women.

Conversely, diabetic women were a significant 62% less likely to develop skin cancer than nondiabetic women.

Men with diabetes had a significant 47% reduction in relative risk for prostate cancer compared with nondiabetic men, but no risk increases for any cancer subtypes were observed in men with versus without diabetes.

The reduction in risk for prostate cancer in diabetic men is supported by previous research, as reported by MedWire News.

“For men, this study is good news,” said Chodick. He added that the opposite is true for women and continued: “The interaction of diabetes and female hormones appears to exaggerate the risk, and make certain organs like the uterus and ovaries more receptive to certain kinds of cancer.”

The authors conclude in the journal Cancer Causes and Control that their results “support the development of primary and secondary prevention programs aimed at women with diabetes and increased awareness of diabetes mellitus patients and healthcare personnel to the importance of cancer prevention efforts.”

Study results show that intensive lifestyle intervention (ILI) reduces cardiovascular disease (CVD) risk factors more than diabetes support and education (DSE), leading to reduced medication use and lower costs.

Previous results from the Look AHEAD (Action for Health in Diabetes) study, reported by MedWire News, showed that ILI improves quality of life, physical fitness, and weight loss more than DSE in overweight individuals with Type 2 diabetes.

In this study, J Bruce Redmon (University of Minnesota, Minneapolis, USA) and colleagues assessed the impact of ILI versus DSE on use and cost of medications for treatment of CVD in 4358 overweight participants of the Look AHEAD trial aged 45–76 years with complete data at 1 year.

DSE involved general recommendations for healthy eating and increased exercise, attendance at an initial session, and invitations to three additional group sessions over the year. The ILI was more intensive than this, including weekly group treatment and monthly individual sessions with a lifestyle counselor.

As previously reported, patients in the ILI group had significantly greater improvements in CVD risk factors at 1 year than those in the DSE group.

In this study, the team compared use of medications to treat diabetes, hypertension, and hyperlipidemia in the ILI and DSE groups at baseline and at 1 year as well as the estimated monthly costs of the medications.

Writing in the journal Diabetes Care, Redmon and co-workers report that patients in the ILI group had significantly lower medication use and costs than those in the DSE group.

At baseline, the Look AHEAD participants were taking an average of 3.3 medications at a monthly cost of approximately US $155 (€129).

At 1 year, the average number of CVD-related medications prescribed to ILI patients was 3.1 versus 3.6 for DSE patients. This corresponds to approximate total monthly costs of $143 (€120) and $173 (€145), respectively.

ILI patients who met optimal care goals at 1 year – glycated hemoglobin below 7%, blood pressure below 130/80 mmHg, and low-density lipoprotein cholesterol below 100 mg/dl – were taking an average of 3.2 medications at a mean monthly cost of $154 (€129). This compared with the DSE patients who were taking 3.8 medications on average at a mean monthly cost of $194 (€163).

“Continued intervention and follow-up will determine whether these changes are maintained and reduce cardiovascular risk,” conclude Redmon et al.

“If these changes can be sustained for the long term, the public health benefits would be substantial,” they add.

Current and initial treatment with the antipsychotic medications olanzapine, clozapine, or mid- and low-potency first-generation antipsychotics (FGA), increases the risk for Type 2 diabetes in schizophrenia patients, report researchers.

However, current aripiprazole treatment was associated with a decreased risk for Type 2 diabetes.

“Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population,” write Jimmi Nielsen (Aarhus University, Aalborg, Denmark) and team in the journalNeuropsychopharmacology.

“Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naive, first-episode patients,” they say.

To address this, they assessed diabetes risks in all (n=7139) antipsychotic-naive patients diagnosed with schizophrenia between January 1997 and December 2004. The participants were followed up for 6.6 years on average for incident Type 2 diabetes.

Over the follow-up period 307 patients developed Type 2 diabetes with an annual incidence rate of 0.65%.

Patients who were older, those taking antihypertensive or lipid-lowering drugs, and those who had initial treatment with olanzapine or mid-potency FGAs had a significantly shorter time to onset of diabetes than individuals who were younger and those not treated with these drugs.

Treatment with low-potency FGAs, olanzapine, or clozapine was associated with increased risk for diabetes within 3 months of diabetes development with odds ratios of 1.52, 1.44, and 1.67, respectively. But aripiprazole treatment reduced the relative risk for incident Type 2 diabetes by 49% compared with no aripiprazole treatment.

“The results from this largest cohort study of antipsychotic-naive schizophrenia patients indicate that in addition to general diabetes risk factors, such as higher age, hypertension, and dyslipidemia… diabetes is promoted by initial treatment with olanzapine and mid-potency FGAs, as well as by current treatment with low-potency FGAs, olanzapine, and clozapine,” summarize Nielsen et al.

They suggest that their results indicate that “educational actions and quality control and improvement initiatives should be taken and studied to improve cardiometabolic outcomes in the vulnerable schizophrenia patients.”

Young adolescents who have been exposed to a hyperinsulinemic environment in the womb are more likely to have the metabolic syndrome or be overweight than those who have not, suggest study results.

Previous research has suggested that offspring of mothers who have gestational diabetes mellitus (GDM) are at increased risk for diabetes and cardiometabolic health problems, say researchers.

To investigate further, Wing Hung Tam (The Chinese University of Hong Kong, China) and colleagues assessed 129 children at 15 years of age for the presence of cardiometabolic risk factors. Of these, 42 were exposed to different severities of GDM in the womb and 87 were not.

Writing in the journal Diabetes Care, Tam and co-workers report that in utero hyperinsulinemia increased the risk for overweight at age 15 years 10-fold after adjusting for birth weight, Tanner staging, maternal GDM status, and maternal body mass index at the follow-up evaluation.

In addition, after adjustment for the same factors, children exposed to GDM were 17 times more likely to develop the metabolic syndrome, as defined by the International Diabetes Foundation criteria with waist circumference and blood pressure cut offs modified to suit the local Chinese population.

The researchers caution that “the present study was limited by a small sample size and is underpowered to detect the effect of maternal GDM on offspring’s abnormal glucose tolerance and other cardiometabolic risks at adolescence.”

They suggest: “A large prospective study extending from early childhood through adolescence into young adulthood will be needed to address the possible effects of in uteroenvironment of maternal GDM and hyperinsulinemia on epigenetic programming and future cardiometabolic risk in the offspring.”