Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

The 10-year prevalence of retinopathy was nearly identical among individuals with impaired fasting glucose as among those with overt diabetes at baseline in a longitudinal French study of 700 adults.

The findings provide further evidence that calls into question the current definition of diabetes, which was based on glycemic thresholds for retinopathy and nephropathy derived from cross-sectional studies conducted in the 1990's.

Dr. Pascale Massin said at the annual meeting of the European Association for the Study of Diabetes (EASD) that recent studies using more sensitive methods for assessing retinopathy are showing that, just as with cardiovascular disease, the relationship between blood glucose and retinopathy varies across a continuum.

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- 

Anemia as a marker. Just a marker!! NEJM, November 19, 2009

A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

 

NEJM, November 19, 2009

 

click here to read more....

 

ABSTRACT

Background Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested.

Methods In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease.

Results Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P=0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P=0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group.

 

Conclusions

• The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event)
• and was associated with an increased risk of stroke.
• For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015 [ClinicalTrials.gov] .)

 

 

Exercise Reverses Aging

Went to a very interesting grand rounds where Dr. Nair discussed some of the research from his lab. The focus of the lab is to assess the effects of aging and whether it is reversible. They found that most proteins seem to have different isoforms and they have developed a new technique (a 2D gel) to differentiate these. Using labeling techniques they showed that these isoforms are age related in that a protein changes with time. They felt these were post-translational changes and maybe due to oxidative damage resulting in poorer function.
They studied physically active individuals and when compared to sedentary subjects, noted that they had significantly less "damaged/aged" muscle.

OBJECTIVE— We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity.

RESEARCH DESIGN AND METHODS— Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18–30 years old) and older (59–76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot.

RESULTS— Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals.

CONCLUSIONS— The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.

Does Size really Matter?

Body Fat Distribution, Adipocyte Size, and Metabolic Characteristics of Nondiabetic Adults

Manpreet S. Mundi, Maksym V. Karpyak, Christina Koutsari, Susanne B. Votruba, Peter C. O'Brien, and Michael D. Jensen^*

Mayo Clinic, Department of Endocrinology, Rochester, Minnesota 55905

^* To whom correspondence should be addressed. E-mail: jensen@mayo.edu.

Context: It is unclear whether adipocyte size or body fat distribution is most strongly linked to the metabolic complications of obesity.

Objective: Our objective was to test whether adipocyte size better predicts metabolic characteristics of obesity than body composition.

Design, Participants, and Setting: We analyzed the relationship between metabolic and anthropometric data collected from 432 largely Caucasian research volunteers (264 women) participating in studies conducted in the Mayo General Clinical Research Center between 1995 and 2008.

Main Outcome Measures: Metabolic variables included fasting plasma glucose, insulin, and triglyceride concentrations. Anthropometric variables included body composition, fat distribution, and sc abdominal and femoral adipocyte size.

Results: Using both univariate and multivariate regression analysis, fasting triglyceride in both men and women was best predicted by computed tomography of visceral fat area. Fasting insulin concentrations were best predicted by sc abdominal fat area in women (r² = 0.40; P <>2 = 0.53; P <> In men, fasting glucose concentrations were predicted by femoral adipocyte size (partial r² = 0.07; P = 0.002), body mass index (partial r² = 0.03; P = 0.07), and age (partial r² = 0.02; P = 0.06). In women, fasting glucose was predicted by abdominal sc fat area (partial r² = 0.12; P <> r² = 0.03; P = 0.01).

Conclusions: Our hypothesis that adipocyte size is the best predictor of metabolic characteristics was not supported in this population. The alternative explanation is that fat mass and body fat distribution have more influence on metabolic responses than adipocyte size.

It's official. Endocrinologists get the ---

From the Endocrine Society:

"CMS has finalized its decision to no longer accept billing for inpatient and outpatient/office consultation services. In place of these codes, physicians will be required to bill codes for either new or established office visits or for initial hospital stays. The Endocrine Society and other physician groups worked extensively to oppose these changes; however, CMS believes that the increase in payment that will be provided for new and established office visits and initial hospital stays will offset losses from the elimination of consultation codes." (emphasis added)

Who cares about the extra 2-3+ years of training, ongoing study and extra board certifcations right? Our services are now indistinguishable from primary care.

"...CMS believes that the increase in payment that will be provided for new and established office visits and initial hospital stays will offset losses from the elimination of consultation codes."

If it will offset it, then why change it to begin with? Is this the sort of short-change we should believe in?

Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

Here is the new update thyroid cancer guidelines.

 

http://www.liebertonline.com/doi/full/10.1089/thy.2009.0110?cookieSet=1

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

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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
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18F-DOPA PET provides superior imaging for pheochromocytoma

6-[F-18]Fluoro-L-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to Conventional Imaging with ¹²³I-Metaiodobenzylguanidine Scintigraphy, Computer Tomography, and Magnetic Resonance Imaging in Localizing Tumors Causing Catecholamine Excess.

Helle-Brit Fiebrich, Adrienne H. Brouwers, Michiel N. Kerstens, Milan E. J. Pijl, Ido P. Kema, Johan R. de Jong, Pieter L. Jager, Philip H. Elsinga, Rudi A. J. O. Dierckx, Jacqueline E. van der Wal, Wim J. Sluiter, Elisabeth G. E. de Vries and Thera P. Links.

The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 10 3922-3930

Abstract:
Context: Catecholamine excess is rare, but symptoms may be life threatening.

Objective: The objective of the study was to investigate the sensitivity of 6-[F-18]fluoro-L-dihydroxyphenylalanine positron emission tomography (¹⁸F-DOPA PET), compared with ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy and computer tomography (CT)/magnetic resonance imaging (MRI) for tumor localization in patients with catecholamine excess.

Design and Setting: All consecutive patients with catecholamine excess visiting the University Medical Center Groningen, Groningen, The Netherlands, between March 2003 and January 2008 were eligible.

Patients: Forty-eight patients were included. The final diagnosis was pheochromocytoma in 40, adrenal hyperplasia in two, paraganglioma in two, ganglioneuroma in one, and unknown in three.

Main Outcome Measures: Sensitivities and discordancy between ¹⁸F-DOPA PET, ¹²³I-MIBG, and CT or MRI were analyzed for individual patients and lesions. Metanephrines and 3-methoxytyramine in plasma and urine and uptake of ¹⁸F-DOPA with PET were measured to determine the whole-body metabolic burden and correlated with biochemical tumor activity. The gold standard was a composite reference standard.

Results: ¹⁸F-DOPA PET showed lesions in 43 patients, ¹²³I-MIBG in 31, and CT/MRI in 32. Patient-based sensitivity for ¹⁸F-DOPA PET, ¹²³I-MIBG, and CT/MRI was 90, 65, and 67% (P <> for ¹⁸F-DOPA PET vs. both ¹²³I-MIBG and CT/MRI, P = 1.0 ¹²³I-MIBG vs. CT/MRI). Lesion-based sensitivities were 73, 48, and 44% (P <>18F-DOPA PET vs. both ¹²³I-MIBG and CT/MRI, P = 0.51 ¹²³I-MIBG vs. CT/MRI). The combination of ¹⁸F-DOPA PET with CT/MRI was superior to ¹²³I-MIBG with CT/MRI (93 vs. 76%, P <> ¹⁸F-DOPA PET correlated with plasma normetanephrine (r = 0.82), urinary normetanephrine (r = 0.84), and metanephrine (r = 0.57).

Conclusion: To localize tumors causing catecholamine excess, ¹⁸F-DOPA PET is superior to ¹²³I-MIBG scintigraphy and CT/MRI.

Comments:
Localizing catecholamine secreting tumors can be notably difficult. This study looked at several imaging modalities in 48 patients with known catecholamine excess. Imaging included 18F-DOPA PET, 123I-MIBG, CT, and MRI.

The highest sensitivity for detecting lesions was 18F-DOPA Pet with CT/MRI which had a 94% sensitivity. 18F-DOPA PET alone had a 72% sensitivity. In contrast, 123I-MIBG with CT/MRI had only a 76% sensitivity. CT/MRI alone was noted to miss mainly adrenal lesions less than 2 cm.

The final histology in patients who received surgery was Pheochromocytoma in 40 patients, adrenal hyperplasia in 2, paraganglioma in 2, ganglioneuroma in 1. 3 remained unknown because no lesions were detected.

At least from this report it appears that combination 18F-DOPA with CT or MRI would be the best way to localize tumor mass in patients with catecholamine excess.

Pancreatic fat and diabetes

Noninvasive Quantification of Pancreatic Fat in Humans

The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 10 4070-4076
Ildiko Lingvay, Victoria Esser, Jaime L. Legendre, Angela L. Price, Kristen M. Wertz, Beverley Adams-Huet, Song Zhang, Roger H. Unger and Lidia S. Szczepaniak

Objective: To validate magnetic resonance spectroscopy (MRS) as a tool for non-invasive quantification of pancreatic triglyceride (TG) content and to measure the pancreatic TG content in a diverse human population with a wide range of body mass index (BMI) and glucose control.

Methods: To validate the MRS method, we measured TG content in the pancreatic tissue of 12 lean and 12 fatty ZDF rats (ages 5–14 weeks) both by MRS and the gold standard biochemical assay. We used MRS to measure pancreatic TG content in vivo in 79 human volunteers. Additionally, to assess the reproducibility of the method, in 33 volunteers we obtained duplicate MRS measurements 1–2 weeks apart.

Results: MRS quantifies pancreatic TG content with high reproducibility and concordance to the biochemical measurement (Spearman’s rank correlation coefficient = 0.91). In humans, median pancreatic TG content was as follows: (1) normal weight and normoglycemic group 0.46 f/w%, (2) overweight or obese but normoglycemic group 3.16 f/w%, (3) impaired fasting glucose or impaired glucose tolerance group (BMI matched with group 2) 5.64 f/w%, and (4) untreated type 2 diabetes group (BMI matched with group 2) 5.54 f/w% (Jonckheere-Terpstra trend test across groups p <>

Conclusions: Human pancreatic steatosis, as measured by MRS, increases with BMI and with impaired glycemia. MRS is a quantitative and reproducible non-invasive clinical research tool which will enable systematic studies of the relationship between ectopic fat accumulation in the pancreas and development of type 2 diabetes.



--------------------

Comments:
How is pancreatic fat related to diabetes/IFG and how is it related to fat deposition in other organs? This intriguing study examines both animal models and humans to help understand the pathophysiology of fat deposition and its relationship to diabetes.

The figure above in A. shows glucose readings along with total pancreatic Triglycerides(pTG) as assessed by magnetic resonance spectroscopy. The pancreatic triglyceride measurements were correlated with a biochemical determination of TG for the rats - Fatty and Lean Zucker rats. There is a progressive increase in pTG along with glucose levels in the Fatty Zucker rats, but no change in either levels in the lean rats. Figure B shows the correlation between the MRS technique and biochemical determination.

Humans were divided into 4 groups and were scanned by MRS as well. The results are as in the abstract. Intereting findings included that blood glucose levels 2 hours after a glucose load were most closely correlated with pTG content. HBA1c, serum Tg, # of DM risk factors, age, BMI, fasting glucose, excercise, and dietary fat intake had either no or a weak relationship to pTG content.

Also of interest was the fact that there was little relationship between pancreatic and hepatic TG content (a previous report had shown a low correlation between hepatic and myocardial TG content).

What is not known is to what degree the TG deposition is related to Beta-cell damage/loss if at all? Also can medications, diet, weight loss or more severe caloric restriction reverse the pancreatic TG deposition and if so can this lead to a new B-cell production?

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