Press Release for Lantus

If you are unable to see the message below, click here to view.

July 14, 2009 On June 26, 2009, four retrospective epidemiologic studies were posted on the Web site of the European Association for the Study of Diabetes (EASD) examining the association of cancer with use of insulins, including Lantus® (insulin glargine [rDNA origin] injection), in patients with diabetes. The EASD had initially received a single study indicating a potential link between Lantus and cancer risk (Hemkens, 2009) but then commissioned three additional studies by other groups to determine the reproducibility of the original observations (Currie, 2009; Jonasson, 2009; SDRN Epidemiology Group, 2009). Rather than providing clear and convincing support for the original study, the four studies taken together provided inconsistent and conflicting information, including analyses refuting a general association of Lantus with excess risk of malignancies. In contrast with controlled clinical trials, which establish and compare well-matched populations given clearly defined treatment regimens, retrospective observational studies (the four studies referenced above) reconstruct cohorts from data extracted from registries not intended for this application, often lacking information critical to establishing matched, clinically relevant comparisons, directly affecting interpretation of results. Sanofi-aventis has monitored the safety of Lantus in preclinical studies and clinical trials prior to market introduction and continues to actively assess risk in the post-marketing setting via active safety surveillance. Extensive experience with Lantus in the 9 years since global market introduction and prior to that in clinical studies has not produced an indication of excess cancer risk:   •   In preclinical studies, there was no evidence that physiologic concentrations of insulin glargine may have a tumor-promoting or even carcinogenic potential (Stammberger, 2002)   •   Controlled clinical trials: -   In studies of up to 1-year duration comprising more than 10,000 patients with type 1 and type 2 diabetes, no significant difference has been observed in the risk of malignancies, including breast cancer, versus other insulin treatments, primarily NPH insulin (Sanofi-aventis, 2009) -   In a 5-year trial in 1017 subjects with type 2 diabetes comparing Lantus and NPH insulin, the occurrence of malignancies, including breast cancer, was similar between groups (Rosenstock, 2009)   •   In uncontrolled studies of more than 60,000 patients with type 1 and type 2 diabetes, the rate of malignancies, including breast cancer, was similar to that reported in the literature (Sanofi-aventis, 2009)   •   In post-marketing safety surveillance, with an estimated global exposure of nearly 24 million patient-years, no specific pattern of malignancies or risk factors has emerged to suggest a newly identified risk with Lantus use (Sanofi-aventis, 2009) A statement from the U.S. Food and Drug Administration (FDA) is consistent with the position and views of other organizations, including the American Diabetes Association and the European Medicines Agency (EMEA), that there are inconsistencies in the findings of these recent registry analyses. The FDA recommends that patients should not stop taking their insulin therapy without consulting a physician, since uncontrolled blood sugar levels can have both immediate and long-term serious adverse effects. The full statement is attached for your reference. A statement from the American Diabetes Association (ADA) notes that the findings from the four retrospective studies are inconclusive, conflicting, and confusing, and cautions against overreaction to the information (ADA, 2009). The statement also makes specific recommendations: Diabetologia, the journal of the European Association for the Study of Diabetes (EASD), published a series of research papers today examining a possible link between insulin glargine (brand name, Lantus) and cancer. Findings from these research papers are conflicting and inconclusive, and the American Diabetes Association cautions against over-reaction until more information is available. Four different population based studies were reported and published in Diabetologia and the data within these studies and between these studies are conflicting and confusing. Until more information is available, the American Diabetes Association advises patients using insulin not to stop taking it. For patients using glargine and considering switching to another form of insulin, the data in these studies make it unclear as to whether any one type of insulin increases the risk of cancer more than other types of insulin. Patients concerned about these studies or their insulin regimen should talk to their doctor and should not stop taking their insulin on the basis of the findings reported here. Insulin is a hormone normally produced by the pancreas that helps the body use glucose for energy. All people with type 1 diabetes need to take insulin to survive; many patients with type 2 diabetes also need to take insulin to control their blood glucose. Glargine insulin, which has been widely used since 2000, is an artificial form of insulin that is typically administered once a day. The American Association of Clinical Endocrinologists (AACE) issued a similar statement (AACE, 2009): On June 26, 2009 several articles published online in Diabetologia by the European Association for the Study of Diabetes investigated the possible relationship between use of insulin glargine (Lantus, sanofi-aventis) and the development of certain malignancies. The authors themselves, and the accompanying editorial, cautioned against over-interpretation of their limited data and analyses, which precluded them from drawing any firm conclusions. For example, there were contradictory findings among the studies, patient populations were not always comparable, and the duration of observation was short. Nonetheless, since the relationship of type 2 diabetes to cancer is of critical importance, further study is warranted. The American Association of Clinical Endocrinologists (AACE) does not recommend that the use of any insulin be changed. AACE supports further research into the effectiveness and safety of all diabetes therapies and will continue to update recommendations as further data becomes available. Individual patient concerns should be discussed with their physicians. For further information, please contact Medical Information Services at 1-800-633-1610 or go to www.factsaboutlantus.com. Sincerely, Michelle A. Baron, MD, F.A.C.E. Vice President, Metabolism Medical Unit U.S. Medical Affairs References:   1.   American Diabetes Association. Statement from the American Diabetes Association related to studies published in 'Diabetologia.' http://www.diabetes.org/for-media/pr-glargine-0602609.jsp. Accessed June 29, 2009.   2.   American Association of Clinical Endocrinologists. AACE response to insulin glargine articles in Diabetologia. http://www.aace.com/newsroom/alerts/index.php. Accessed June 29, 2009.   3.   Currie CJ, Poole CD, Gale EAM. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009. Epub ahead of print.   4.   Hemkens LG, Grouven U, Bender R, et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia. 2009. Epub ahead of print.   5.   Jonasson JM, Ljung R, Talbäck M, Haglund B, Gudbjörnsdòttir S, Steineck G. Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden. Diabetologia. 2009. Epub ahead of print.   6.   Rosenstock J, Fonseca V, McGill JB, et al. Similar progression of diabetic retinopathy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study. Diabetologia. 2009. Epub ahead of print.   7.   Sanofi-aventis. Sanofi-aventis stands behind the safety of Lantus® [press release]. Paris, France: June 26, 2009.   8.   SDRN Epidemiology Group. Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia. 2009. Epub ahead of print.   9.   Stammberger I, Bube A, Durchfeld-Meyer B, Donaubauer H, Troschau G. Evaluation of the carcinogenic potential of insulin glargine (LANTUS) in rats and mice. Int J Toxicol. 2002;21(3):171-179. Early Communication About Safety of Lantus (insulin glargine) 7/1/2009 FDA is aware of four recently-published observational studies that looked at the use of Lantus (insulin glargine) and possible risk for cancer in patients with diabetes. Three of the four studies suggest an increased risk for cancer associated with use of Lantus. See http://www.diabetologia-journal.org/cancer.html. Based on the currently available data, the FDA recommends that patients should not stop taking their insulin therapy without consulting a physician, since uncontrolled blood sugar levels can have both immediate and long-term serious adverse effects. Patients should also contact their healthcare professional if they have concerns about the medicines they are taking. Similar to human insulin, insulin glargine is used to control blood sugar in people with Type 1 and Type 2 diabetes. Insulin glargine, however, is a modified version of human insulin (an insulin analogue) that allows for the control of blood sugar for extended periods of time (a long-acting insulin). Insulin glargine is approved for once-a-day dosage by subcutaneous injection (injection under the skin). The four observational studies evaluated large patient databases and all reported some level of association between the use of insulin glargine, and other insulin products, and various types of cancer. The duration of patient follow-up in all four studies was shorter than what is generally considered necessary to evaluate for cancer risk from drug exposure. Further, inconsistencies in findings within and across individual studies raise concerns as to whether an association between the use of insulin glargine and cancer truly exists. Additionally, differences in patient characteristics across the treatment groups may have contributed to a finding of increased cancer risk. FDA is currently reviewing many sources of safety data for Lantus, including these newly published observational studies, data from all completed controlled clinical trials, and information about ongoing controlled clinical trials, to better understand the risk, if any, for cancer associated with use of Lantus. Discussions are also ongoing between FDA and the manufacturer of Lantus as to whether any additional studies evaluating the safety and efficacy of this drug will need to be performed. FDA will communicate the results on its ongoing review to the public, as appropriate, as our review continues. The FDA encourages both healthcare professionals and patients to report side effects from the use of insulin glargine to the FDA's MedWatch Adverse Event Reporting Program using the information at the bottom of the page. This early communication is in keeping with FDA's commitment to informing the public about its ongoing safety reviews of drugs. FDA will communicate its findings with the public as soon as its review of insulin glargine is complete. This information reflects FDA's current analysis of available data concerning this drug. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing this product. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available. Please do not reply to this email. We cannot accept electronic replies to this email address. sanofi-aventis, 55 Corporate Dr., Bridgewater, NJ 08807-1265

 

This e-mail powered by Med-E-Mail connects physicians with relevant commercial messages germane to the practice of medicine.
If you wish to discontinue receiving messages from this sender please review your preference page here.

--
Dr. Wei-An Andy Lee
Clinical Endocrinologist
Assistant Professor of Clinical Medicine
Keck School of Medicine
University of Southern California

"This email message is confidential, intended only for the recipient(s) named above and
may contain information this is privileged, exempt from disclosure under applicable law.
If you are not the intended recipient, do not disclose or disseminate this message to
anyone except the intended recipient. If you have received this message in error, or are
not the named recipient(s), please immediately notify the sender by return email, and
delete all copies of this message."

Intensive glucose control in DM1 and long term risk of impaired GFR

Intensive Diabetes Therapy and GFR in Type 1 Diabetes

The DCCT/EDIC Research Group*

NEJM Nov 12, 2011

Abstract

BACKGROUND

An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.

METHODS

In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m² of body-surface area at two consecutive study visits.

RESULTS

Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m² during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m² (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates.

CONCLUSIONS

The long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy.

Key facts:

• Briefly, intensive therapy consisted of three or more injections of insulin daily or the use of an insulin pump, with the aim of achieving a glycated hemoglobin level of less than 6.05% (which was considered to be the upper limit of the normal range). The goal of conventional therapy was the prevention of symptoms of hyperglycemia and hypoglycemia with the use of one or two injections of insulin daily.

• The mean glycated hemoglobin level during the DCCT (1983 through 1993), time-averaged throughout the study, was 7.3% in the intensive-therapy group and 9.1% in the conventional-therapy group.

• The median follow-up period for the two studies combined was 22 years (interquartile range, 21 to 24). During this time, impairment of the GFR developed in 70 participants, of whom 24 had been assigned to DCCT intensive therapy and 46 to DCCT conventional therapy

• Our data suggest that giving approximately 29 persons with type 1 diabetes intensive diabetes therapy for 6.5 years prevents one case of an impaired GFR over a total follow-up period of 20 years.

• Moreover, along with congruent salutary effects on retinopathy, neuropathy, and cardiovascular disease, these effects reinforce current recommendations to target a glycated hemoglobin level of less than 7% in patients with type 1 diabetes.10,11

[43] Impact of food insecurity on Diabetes self management

Impact of food insecurity on Diabetes self management

#MP111212
[Lyles, Diabetes Care, 12, food insecurity, diabetes self management, 0.38%]
http://www.ncbi.nlm.nih.gov/pubmed/23275354

Diabetes Care. 2012 Dec 28. [Epub ahead of print]

Food Insecurity in Relation to Changes in Hemoglobin A1C, Self-Efficacy, and Fruit/Vegetable Intake During a Diabetes Educational Intervention.

Lyles CR, Wolf MS, Schillinger D, Davis TC, Dewalt D, Dahlke AR, Curtis L, Seligman HK.

Source

University of California San Francisco Center for Vulnerable Populations, Division of General Internal Medicine at San Francisco General Hospital, San Francisco, California.

Abstract

OBJECTIVE Food insecurity is hypothesized to make diabetes self-management more difficult. We conducted a longitudinal assessment of food insecurity with several diabetes self-care measures.RESEARCH DESIGN AND METHODSWe conducted a secondary, observational analysis of 665 low-income patients with diabetes, all of whom received self-management support as part of a larger diabetes educational intervention. We analyzed baseline food insecurity (measured by the U.S. Department of Agriculture Food Security module) in relation to changes in hemoglobin A1C (HbA(1c)) as well as self-reported diabetes self-efficacy and daily fruit and vegetable intake. We examined longitudinal differences using generalized estimating equation linear regression models, controlling for time, age, sex, race, income, and intervention arm.RESULTSOverall, 57% of the sample had an income <$15,000. Participants who were food insecure (33%) were younger, had less income, and were more likely to be unemployed compared with participants who were food secure. At baseline, those who were food insecure had higher mean HbA(1c) values (8.4% vs. 8.0%) and lower self-efficacy and fruit and vegetable intake than those who were food secure (all P < 0.05). Compared with food-secure individuals, participants who were food insecure had significantly greater improvements in HbA(1c) over time (0.38% decrease compared with 0.01% decrease; P value for interaction <0.05) as well as in self-efficacy (P value for interaction <0.01). There was no significant difference in HbA(1c) by food security status at follow-up.CONCLUSIONSParticipants experiencing food insecurity had poorer diabetes-related measures at baseline but made significant improvements in HbA(1c) and self-efficacy. Low-income patients who were food insecure may be particularly receptive to diabetes self-management support, even if interventions are not explicitly structured to address finances or food security challenges.

[20] 20th article and 200 yrs nejm

Andy Lee (@drandylee) 11/25/12 11:15 PM #mp111212 History of dm [polonsky, nejm, 12, 1500, aretaeus, 1812] 20th article milestone!! nejm.org/doi/full/10.10… Unfortunately, the improvement in outcomes for individual patients with diabetes has not resulted in similar improvements from the public health perspective.  The worldwide prevalence of diabetes has continued to increase dramatically. The difficulty in applying the principles of diabetes care from the individual patient to the population reflects the unique challenges of implementing research findings and effecting behavioral change.  Figure 4 shows the number and percentage of persons in the U.S. population with diagnosed diabetes between 1980 and 2010 (http://www.cdc.gov/diabetes/statistics/prevalence_national.htm).  During this period, the number of diagnosed cases of diabetes increased from 5.6 million to 20.9 million, representing 2.5% and 6.9% of the population, respectively.  Nearly 27% of persons over 65 years of age have diabetes. If current trends continue, 1 in 3 U.S. adults could have diabetes by 2050.  The American Diabetes Association estimated that the cost of diagnosed diabetes in the United States was $174 billion in 2007,50 and efforts to prevent and treat diabetes threaten to overwhelm health systems throughout the world. Great link for a history of diabetes.....link

ddiabetes
eepi

Intensive Glucose Control and Cardiovascular Outcomes in Type 2 Diabetes (April 2010). Macisaac RJ, Jerums G.

Heart Lung Circ. 2010 Aug 29. [Epub ahead of print]

Intensive Glucose Control and Cardiovascular Outcomes in Type 2 Diabetes (April 2010).http://www.ncbi.nlm.nih.gov/pubmed/20807681

Macisaac RJ, Jerums G.

Endocrine Centre and Department of Medicine, Austin Health and University of Melbourne, Australia.

Abstract

Numerous observational studies have clearly shown a relationship between hyperglycaemia and cardiovascular (CV) disease. However, the United Kingdom Prospective Diabetes Study (UKPDS), which involved subjects with newly diagnosed type 2 diabetes, just failed to show that intensive glucose control significantly reduces CV events. The results of three subsequent large randomised controlled trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) and the Veterans Administration Diabetes Trial (VADT), that involved approximately 25,000 subjects with established type 2 diabetes also failed to show that intensive glucose control, aiming for a glycated haemoglobin (HbA(1c)) level<7%, significantly reduces CV events. The ACCORD trial even suggested that under certain circumstances, intensive glucose control is associated with an increased risk for CV and all-cause mortality. Although the exact mechanisms responsible for an increase in mortality in the ACCORD trial remain unknown, there was an association between increased rates of mortality with higher rates of severe hypoglycaemia in the intensive glucose control group. In contrast, a 10-year post-randomisation follow-up study of the tight glucose intervention arm of the UKPDS showed that intensive glucose control was associated with a significant reduction in the risk for myocardial infarction (MI), diabetes-related deaths and all-cause mortality. This suggests that early strict glucose control generates a legacy effect that is eventually translated into protection from CV events. Recent meta-analyses of the above randomised trails have also shown that intensive glucose control is associated with a reduced risk of MI, without a clear benefit on other CV diseases such as stroke. Furthermore, these analyses have also shown that intensive glucose control is associated with increased rates of severe hypoglycaemia but not increased rates of CV or all-cause mortality. Aiming for HbA(1c) levels of <7.0% still remains the general target for good glucose control. Under certain circumstances, aiming for lower HbA(1c) levels may be appropriate. This applies in the setting of newly diagnosed diabetes in relatively young individuals without significant co-morbidities and in patients treated with agents that minimize the risk of severe hypoglycaemia such as metformin. Whether this also applies to newer glucose-lowering agents that target the incretin system will depend on CV outcomes of long-term studies which are in progress.

--
Dr. Wei-An Andy Lee
Clinical Endocrinologist
Assistant Professor of Clinical Medicine
Keck School of Medicine
University of Southern California

"This email message is confidential, intended only for the recipient(s) named above and
may contain information this is privileged, exempt from disclosure under applicable law.
If you are not the intended recipient, do not disclose or disseminate this message to
anyone except the intended recipient. If you have received this message in error, or are
not the named recipient(s), please immediately notify the sender by return email, and
delete all copies of this message."

Diabetes on the Rise. Data from the CDC.

Just some numbers to keep in mind for diabetes prevalence.


Prevalence of diagnosed and undiagnosed diabetes in the United States, all ages, 2007
Total: 23.6 million people or 7.8% of the population have diabetes.
Diagnosed: 17.9 million people
Undiagnosed: 5.7 million people
Prevalence of diagnosed and undiagnosed diabetes among people aged 20 years or older,
United States, 2007
Age 20 years or older: 23.5 million or 10.7% of all people in this age group have diabetes.
Age 60 years or older: 12.2 million or 23.1% of all people in this age group have diabetes.
Men: 12.0 million or 11.2% of all men aged 20 years or older have diabetes.
Women: 11.5 million or 10.2% of all women aged 20 years or older have diabetes.

The full pdf from the CDC.  read in goodreader.

Andy

--
Dr. Wei-An Andy Lee
Clinical Endocrinologist
Assistant Professor of Clinical Medicine
Keck School of Medicine
University of Southern California

"This email message is confidential, intended only for the recipient(s) named above and
may contain information this is privileged, exempt from disclosure under applicable law.
If you are not the intended recipient, do not disclose or disseminate this message to
anyone except the intended recipient. If you have received this message in error, or are
not the named recipient(s), please immediately notify the sender by return email, and
delete all copies of this message."

How much better is genetic analysis over family history?

Clinical Risk Factors, DNA Variants, and the Development of Type 2 Diabetes

Valeriya Lyssenko, M.D., Anna Jonsson, M.Sc., Peter Almgren, M.Sc., Nicoló Pulizzi, M.D., Bo Isomaa, M.D., Tiinamaija Tuomi, M.D., Göran Berglund, M.D., David Altshuler, M.D., Peter Nilsson, M.D., and Leif Groop, M.D.

ABSTRACT

Background Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts.

Methods We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time.

Results Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10–4). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased.

Conclusions
As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up.

Hypogonadism and Diabetes

I recently had to review a paper on the topic of hypogonadism an diabetes and came across an entire topic that I was not aware of. There has been extensive research done looking at the association between testosterone (free and total), SHBG, and the development of diabetes.

A number of things affect both SHBG as well as testosterone. Age, exercise, obesity just to name a few. However, insulin also affects SHBG levels. Hyperinsulinemia is associated with a reduction in SHBG concentration and SHBG concentration is positively associated with insulin sensitivity. SHBG concentration is also negatively correlated with insulin resistance, insulin levels and glucose concentration. Both insulin and insulin-like growth factor 1 have inhibitory effects on SHBG secretion by Hep G2 cells in vitro. Insulin also suppresses hepatic SHBG synthesis.

Because of this relationship, many papers are studying whether SHBG levels can be predictive of the development of diabetes. Because SHBG binds to its receptor and actually has some actions through g-protein/cAMP pathway, there are studies also looking at whether low levels of SHBG may actually lead to diabetes. If this pans out, perhaps SHBG may be a target in the future for something else we have to raise.

Further Reading:

1. Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care. 2000;23(4):490-494.

This article shows that there is a Odds ratio of 1.89 of developing diabetes with a 1SD reduction in SHBG concentration.

2. Nair KS, Rizza RA, O'Brien P, et al. DHEA in Elderly Women and DHEA or Testosterone in Elderly Men. N Engl J Med. 2006;355(16):1647-1659.

From the WFMC...this article shows what little effect treating the elderly with DHEA in women or testosterone in men had on inuslin sensitivity.

3. Betancourt-Albrecht M, Cunningham GR. Hypogonadism and diabetes. Int. J. Impot. Res. 2003;15 Suppl 4:S14-20.

A pretty good review article on the topic.

Statin-Induced Diabetes: Will It Change Clinical Practice?

1. L. Maria Belalcazar, MD¹,
2. Vasudevan A. Raghavan, MBBS, MD, MRCP² and
3. Christie M. Ballantyne, MD³

+ Author Affiliations

1. ¹Department of Medicine, University of Texas Medical Branch, Galveston, Texas;
2. ²Division of Endocrinology, Diabetes and Metabolism, Scott and White Hospitals/Texas A&M Health Science Center, Temple, Texas;
3. ³Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Texas.

1. Corresponding author: Christie M. Ballantyne, cmb@bcm.tmc.edu.

An increase in the incidence of physician-diagnosed diabetes with rosuvastatin in Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) published recently revived clinical interest in the effects of statins on glycemic control. The study showed that, after almost 2 years of follow-up in men and women with elevated levels of high-sensitivity C-reactive protein but average LDL cholesterol, rosuvastatin therapy was associated with a mild but significant increase in the identification of new-onset diabetes (3% in the statin arm, 2.4% in the placebo arm; P < 0.01) (1). The potential association between statin use and new-onset diabetes gained attention in 2001 when a post hoc analysis of another primary prevention statin trial, the West of Scotland Coronary Prevention Study (WOSCOPS), reported that treatment with pravastatin decreased the hazard of developing type 2 diabetes by 30% (hazard ratio 0.7 [95% CI 0.5–0.99]; P = 0.042) (2). These seemingly contradictory findings flank results from four other statin trials that failed to uncover a significant relationship between statin use and incident type 2 diabetes when the latter was evaluated as a tertiary end point (3–6).

 

click here to read more....

The rationale for the diagnosis of diabetes in questions!

Lancet. 2008 Mar 1;371(9614):736-43.

Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies.

Wong TY, Liew G, Tapp RJ, Schmidt MI, Wang JJ, Mitchell P, Klein R, Klein BE, Zimmet P, Shaw J.

Centre for Eye Research Australia, University of Melbourne, VIC, Australia. twong@unimelb.edu.au

Erratum in:

• Lancet. 2008 May 31;371(9627):1838.

Comment in:

• Lancet. 2008 Mar 1;371(9614):700-2.

BACKGROUND: The WHO and American Diabetes Association criteria for diagnosing diabetes mellitus assume the presence of a glycaemic threshold with high sensitivity for identifying retinopathy. However, this assumption is based on data from three previous studies that had important limitations in detecting retinopathy. We aimed to provide updated data for the relation between fasting plasma glucose (FPG) and retinopathy, and to assess the diagnostic accuracy of current FPG thresholds in identifying both prevalent and incident retinopathy. METHODS: We examined the data from three cross-sectional adult populations: those in the Blue Mountains Eye Study (BMES, Australia, n=3162), the Australian Diabetes, Obesity and Lifestyle Study (AusDiab, Australia, n=2182), and the Multi-Ethnic Study of Atherosclerosis (MESA, USA, n=6079). Retinopathy was diagnosed from multiple retinal photographs of each eye, and graded according to the modified Airlie House Classification system. Plasma glucose concentrations were measured from fasting venous blood samples. FINDINGS: The overall prevalence of retinopathy was 11.5% in BMES (95% CI 10.4-12.6%), 9.6% in AusDiab (8.4-10.9), and 15.8% in MESA (14.9-16.7). 

However, we found inconsistent evidence of a uniform glycaemic threshold for prevalent and incident retinopathy, with analyses suggesting a continuous relation. 

The widely used diabetes FPG cutoff of 7.0 mmol/L or higher had sensitivity less than 40% (range 14.8-39.1) for detecting retinopathy, with specificity between 80.8% and 95.8%. The area under receiver operating characteristic curves for FPG and retinopathy was low and ranged from 0.56 to 0.61. INTERPRETATION: We saw no evidence of a clear and consistent glycaemic threshold for the presence or incidence of retinopathy across different populations. The current FPG cutoff of 7.0 mmol/L used to diagnose diabetes did not accurately identify people with and without retinopathy. 

These findings suggest that the criteria for diagnosing diabetes could need reassessment- 

Some Insulin-Producing Beta Cells May Persist In Long-Term Type 1 Diabetes Survivors.

Some Insulin-Producing Beta Cells May Persist In Long-Term Type 1 Diabetes Survivors.

HealthDay (8/18, Gordon) reported that, according to a study published online Aug. 10 in the journal Diabetes, "the insulin-producing beta cells destroyed by type 1 diabetes may actually be in a constant state of turnover, even in people who've had diabetes for decades." Researchers arrived at that conclusion after studying 114 people who had survived with type 1 diabetes for at least 50 years and conducting "a post-mortem pancreas analysis from another nine" people who had had type 1 diabetes for that time. The study's lead author stated, "In our study, we made the unexpected finding that about two-thirds of the [study participants] still retained the ability to have positive C-peptide results, which is an indication that they could still be making insulin."

--
Dr. Wei-An Andy Lee
Clinical Endocrinologist
Assistant Professor of Clinical Medicine
Keck School of Medicine
University of Southern California

"This email message is confidential, intended only for the recipient(s) named above and
may contain information this is privileged, exempt from disclosure under applicable law.
If you are not the intended recipient, do not disclose or disseminate this message to
anyone except the intended recipient. If you have received this message in error, or are
not the named recipient(s), please immediately notify the sender by return email, and
delete all copies of this message."

Legacy Effect not for Blood Pressure

Long-Term Follow-up after Tight Control of Blood Pressure in Type 2 Diabetes
Rury R. Holman, F.R.C.P., Sanjoy K. Paul, Ph.D., M. Angelyn Bethel, M.D., H. Andrew W. Neil, F.R.C.P., and David R. Matthews, F.R.C.P.

NEJM, Volume 359:1565-1576, october, 2008

ABSTRACT
Background
Post-trial monitoring of patients in the United Kingdom Prospective Diabetes Study (UKPDS) examined whether risk reductions for microvascular and macrovascular disease, achieved with the use of improved blood-pressure control during the trial, would be sustained.

Methods Among 5102 UKPDS patients with newly diagnosed type 2 diabetes mellitus, we randomly assigned, over a 4-year period beginning in 1987, 1148 patients with hypertension to tight or less-tight blood-pressure control regimens. The 884 patients who underwent post-trial monitoring were asked to attend annual UKPDS clinics for the first 5 years, but no attempt was made to maintain their previously assigned therapies. Annual questionnaires completed by patients and general practitioners were used to follow patients who were unable to attend the clinic in years 1 through 5, and questionnaires were used for all patients in years 6 to 10. Seven prespecified aggregate clinical end points were examined on an intention-to-treat basis, according to the previous randomization categories.

Results Differences in blood pressure between the two groups during the trial disappeared within 2 years after termination of the trial. Significant relative risk reductions found during the trial for any diabetes-related end point, diabetes-related death, microvascular disease, and stroke in the group receiving tight, as compared with less tight, blood-pressure control were not sustained during the post-trial follow-up. No risk reductions were seen during or after the trial for myocardial infarction or death from any cause, but a risk reduction for peripheral vascular disease associated with tight blood-pressure control became significant (P=0.02).

Conclusions The benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost. Early improvement in blood-pressure control in patients with both type 2 diabetes and hypertension was associated with a reduced risk of complications, but it appears that good blood-pressure control must be continued if the benefits are to be maintained.

[37] How does metformin reduce cancers?

[Akin,Clin Endocrinology, 12,Metformin, Pigment epithelium derived factor, insulin resistance]

Clin Endocrinol (Oxf). 2012 Dec;77(6):852-6. doi: 10.1111/j.1365-2265.2012.04341.x.

#mp111212

Pigment epithelium-derived factor increases in type 2 diabetes after treatment with metformin.

Akın S, Aksoy DY, Cınar N, Aydın K, Karaağaoğlu E, Arıyürek M, Gülçelik NE, Usman A, Gürlek A.

Source

Section of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Hacettepe University.

Abstract

OBJECTIVE:

Pigment epithelium-derived factor (PEDF) has anti-angiogenic, immunomodulatory and anti-inflammatory properties. In addition to the significant role it plays in reducing diabetic complications, PEDF is now used in the treatment of certain cancers. It possibly plays a role in insulin resistance cases, too. However, whether metformin treatment has any significant effects on PEDF levels is not known. In this study, we investigated the regulation of PEDF in type 2 diabetes in relation to fat mass and insulin resistance before and after the use of metformin for treatment.

DESIGN:

Prospective cohort study.

SUBJECTS:

Thirty-six patients with newly diagnosed type 2 diabetes and 33 healthy individuals.

MEASUREMENTS:

Baseline weight, waist circumference (WC), fasting (FPG) and postprandial (PPPG) glucose, insulin, HbA1c, HOMA, PEDF and total/truncal fat mass were determined both in the diabetic and control subjects. Procedures were repeated in the diabetic group after a 6-month metformin treatment.

RESULTS:

Baseline FPG, PPPG, HbA1c, HOMA, weight, WC and truncal fat mass were higher in patients with diabetes whereas PEDF levels were found to be comparable with the controls. We completed the study with 31 of the 36 patients with diabetes we had selected for the study. We observed a decrease in the weight, WC, FPG, PPPG, HOMA, total and truncal fat mass of the patients while there was a significant rise in the PEDF levels (P = 0·002) after the metformin treatment. On the other hand, no significant correlation was observed between the change in PEDF levels and the clinical and laboratory findings.

CONCLUSION:

Our study is the first to identify a metformin-related increase in PEDF levels in diabetes. The increase observed in PEDF levels after the metformin treatment does not seem to be related to the changes in insulin resistance, fat mass or glycemic control. Hence, our results suggest that further investigation is necessary to determine the direct effects of metformin on PEDF gene and protein expression in vitro.

Byetta extend life?

Lilly Diabetes Drug Shows a Life-Extending Promise
By ALEX BERENSON

Can Byetta, an injectable drug that lowers blood sugar, really help people with diabetes to live longer?

Possibly, according to the results of a major clinical trial presented at the American Diabetes Association annual conference. In the trial, called Accord, patients with Type 2 diabetes were prescribed Byetta or any of several other diabetes medicines. Patients who took Byetta had a much lower chance of dying, about 75 percent lower, than those who took any other drug.

The finding, presented in June, has generated a stir among diabetes researchers, although so far it has attracted little public notice. Neither Eli Lilly or Amylin, the companies that jointly market Byetta, is publicizing the findings, in part because no one is sure whether the reduction in the death rate is real or a chance finding. Only about 825 patients in the 10,000-patient Accord trial took Byetta, and those who did were likelier to be healthier than other patients.

Read more....

Bromocriptine and diabetes

Diabetes Care. 2000 Aug;23(8):1154-61. Links

Bromocriptine: a novel approach to the treatment of type 2 diabetes.

OBJECTIVE:

• In vertebrates, body fat stores and insulin action are controlled by the temporal interaction of circadian neuroendocrine oscillations.
• Bromocriptine modulates neurotransmitter action in the brain and has been shown to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes.
• We studied the effect of a quick-release bromocriptine formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS:
There were 22 obese subjects with type 2 diabetes
randomized to receive a quick-release formulation of bromocriptine (n = 15) or placebo (n = 7) in a 16-week double-blind study.
Subjects were prescribed a weight-maintaining diet to exclude any effect of changes in body weight on the primary outcome measurements.
Fasting plasma glucose concentration and HbA(1c) were measured at 2- to 4-week intervals during treatment.
Body composition (underwater weighing), body fat distribution (magnetic resonance imaging), oral glucose tolerance (oral glucose tolerance test [OGTT]), insulin-mediated glucose disposal, and endogenous glucose production (2-step euglycemic insulin clamp, 40 and 160 mU x min(-1) x m(-2)) were measured before and after treatment.

RESULTS:
No changes in body weight or body composition occurred during the study in either placebo- or bromocriptine-treated subjects.
Bromocriptine significantly reduced HbA(1c) (from 8.7 to 8.1%, P = 0.009) and fasting plasma glucose (from 190 to 172 mg/dl, P = 0.02) levels, whereas these variables increased during placebo treatment (from 8.5 to 9.1%, NS, and from 187 to 223 mg/dl, P = 0.02, respectively). The differences in HbA(1c) (delta = 1.2%, P = 0.01) and fasting glucose (delta = 54 mg/dl, P < 0.001) levels between the bromocriptine and placebo group at 16 weeks were highly significant.
The mean plasma glucose concentration during OGTT was significantly reduced by bromocriptine (from 294 to 272 mg/dl, P = 0.005), whereas it increased in the placebo group. No change in glucose disposal occurred during the first step of the insulin clamp in either the bromocriptine- or placebo-treated group.
During the second insulin clamp step, bromocriptine improved total glucose disposal from 6.8 to 8.4 mg x min(-1) kg(-1) fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg min(-1) x kg(-1) FFM (P < 0.05), whereas both of these variables deteriorated significantly (P < or = 0.02) in the placebo group.

CONCLUSIONS: Bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients. Both reductions in fasting and postprandial plasma glucose levels appear to contribute to the improvement in glucose tolerance. The bromocriptine-induced improvement in glycemic control is associated with enhanced maximally stimulated insulin-mediated glucose disposal.