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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_394"
                     title="Even Normal Glucose in Kids Could Predict Diabetes Later (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/Endocrinology/Diabetes/tb/18291?impressionId=1265754969053"
                     
      Increases in fasting plasma glucose during childhood  --  even though levels remain in the normal range  --  can predict adult prediabetes and type 2 diabetes later in life, a retrospective cohort study showed.&lt;br&gt;
&lt;br&gt;Among individuals with a fasting plasma glucose of less than 100 mg/dL as children, increasing levels were associated with greater risks of prediabetes (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and type 2 diabetes (&lt;em&gt;P&lt;/em&gt;=0.03) in adulthood, according to Gerald Berenson, MD, of Tulane University Health Sciences Center in New Orleans, and colleagues.&lt;br&gt;
&lt;br&gt;There appeared to be a threshold  --  85 mg/dL  --  above which the risk of adult problems began to increase, the researchers reported in the February issue of &lt;em&gt;Archives of Pediatrics and Adolescent Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;It is not surprising that a higher fasting glucose level in childhood predicts prediabetes and diabetes in adulthood,&quot; Matthew Gillman, MD, of Harvard, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;More surprising, he said, was the existence of the apparent threshold, although &quot;the authors are appropriately circumspect about recommending lowering glucose cutoff points to diagnose children at risk of developing prediabetes or diabetes.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Even if there is a threshold over which children are at substantially higher risk of later prediabetes, it is unclear exactly how high the risk should be to make changing guidelines a good thing,&quot; he wrote. &quot;After all, the right interventions for individuals with prediabetes are still obscure, so identifying more of them may be more trouble than it&apos;s worth.&quot;&lt;/p&gt;
&lt;p&gt;According to Berenson and colleagues, 19 million U.S. adults have type 2 diabetes. More common is a prediabetic state of impaired fasting glucose, affecting about 54 million.&lt;/p&gt;
&lt;p&gt;Previous studies have suggested that higher plasma glucose levels, even if still in the normal range, might be a predictor of diabetes.&lt;/p&gt;
&lt;p&gt;Berenson&apos;s group wanted to see whether elevated fasting plasma glucose in childhood would predict prediabetes or type 2 diabetes in adulthood.&lt;/p&gt;
&lt;p&gt;To find out, they turned to the Bogalusa Heart Study, which began tracking children from that Louisiana town in 1978. All had a fasting plasma glucose lower than 100 mg/dL.&lt;/p&gt;
&lt;p&gt;The current analysis included those same individuals assessed as adults after a mean follow-up of 21 years  --  1,723 were normoglycemic (99 mg/dL or lower), 79 were prediabetic (100 to 125 mg/dL), and 47 had type 2 diabetes.&lt;/p&gt;
&lt;p&gt;Using a childhood fasting plasma glucose of 86 mg/dL or higher as a predictor for prediabetes yielded a 76.9% sensitivity and 85.2% specificity. For diabetes, sensitivity was 75% and specificity was 76%.&lt;/p&gt;
&lt;p&gt;In a multivariate analysis controlling for anthropometric, hemodynamic, and metabolic variables from childhood to adulthood, as well as baseline fasting plasma glucose level, those individuals who had a childhood level 86 mg/dL or higher had increased risks of both prediabetes (OR 3.40, 95% CI 1.87 to 6.18) and type 2 diabetes (OR 2.06, 95% CI 1.01 to 4.23) as adults.&lt;/p&gt;
&lt;p&gt;The authors acknowledged some limitations of the study, including the lack of data on postchallenge glucose, in vivo insulin action and secretion, and glycosylated hemoglobin in childhood.&lt;/p&gt;
&lt;p&gt;Gillman, the editorialist, also noted that the findings&apos; generalizability to children today is unclear because obesity was much less prevalent when the adults in this study were children.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by grants from the National Institute on Aging and the American Heart Association.&lt;/p&gt;&lt;p&gt;The editorial was supported by a grant from the NIH.&lt;/p&gt;&lt;p&gt;Neither the study authors nor the editorialist reported any conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_391"
                     title="Rare Genetic Deletion Linked to Morbid Obesity (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/Genetics/GeneralGenetics/tb/18286?impressionId=1265754969053"
                     
      &lt;p&gt;Missing sections of DNA may have a powerful impact on weight for a small segment of the population, researchers said.&lt;/p&gt;
&lt;p&gt;Nearly all teens and adults found to have a particular deletion of roughly 30-genes on chromosome 16p11.2 were obese  --  most morbidly so  --  with a body mass index of at least 40 kg/m&lt;sup&gt;2&lt;/sup&gt;, Philippe Froguel, MD, PhD, of Imperial College London, and colleagues reported in &lt;em&gt;Nature&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;While the variant appeared to explain only a small proportion of morbid obesity  --  0.7% in the study population  --  it was never present in healthy, normal-weight controls.&lt;/p&gt;
&lt;p&gt;&quot;Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic,&quot; Froguel said in a prepared statement.&lt;/p&gt;
&lt;p&gt;But with further findings like these, it may be possible to identify such individuals through genetic testing, he said.&lt;/p&gt;
&lt;p&gt;If so, &quot;We can then offer them appropriate support and medical interventions, such as the option of weight-loss surgery, to improve their long-term health,&quot; Froguel declared.&lt;/p&gt;
&lt;p&gt;Although researchers speculate that one in 20 cases of obesity may have a genetic cause, the genetic component remains largely elusive.&lt;/p&gt;
&lt;p&gt;Even accounting for such a small fraction of cases, the newly discovered 16p11.2 variant would be the second most frequent known genetic cause of obesity, Froguel&apos;s group said.&lt;/p&gt;
&lt;p&gt;Extensive genome-wide association studies have linked numerous single nucleotide polymorphisms (SNPs) to obesity, but added all together they account for only a small fraction of the known heritable component, the researchers said.&lt;/p&gt;
&lt;p&gt;&quot;The &apos;common disease, common variant&apos; hypothesis is increasingly coming under challenge,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Their team first identified the genetic deletion in teen and adults with learning difficulties or delayed development.&lt;/p&gt;
&lt;p&gt;Because the 31 individuals who had the nearly identical deletions of at least 593 kilobases at chromosome 16p11.2 in one copy of their DNA all had a BMI of over 30 kg/m&lt;sup&gt;2&lt;/sup&gt;, the researchers decided to dig a little deeper.&lt;/p&gt;
&lt;p&gt;&quot;Cohorts with extreme phenotypes that include obesity may be enriched for rare but very potent risk variants,&quot; making them easier to discover, they wrote.&lt;/p&gt;
&lt;p&gt;So they undertook a case-control study among 312 patients at three centers in Britain and France who presented with congenital malformations, developmental delay, or both, in addition to obesity.&lt;/p&gt;
&lt;p&gt;The same deletions were seen in 2.9% of these individuals.&lt;/p&gt;
&lt;p&gt;The function of the missing genes are not well known, but some have previously been associated with delayed development, autism, and schizophrenia.&lt;/p&gt;
&lt;p&gt;Notably, though, the frequency of deletion of these genes in the obese case-control cohort was &quot;appreciably higher&quot; than the less than 1% seen in the autism and other studies that didn&apos;t include obesity as an inclusion criteria, the researchers said.&lt;/p&gt;
&lt;p&gt;A second independent survey of genetic data at eight cytogenetic centers in France, Switzerland, and Estonia turned up a 0.6% rate among 3,947 people with developmental delay, malformations, or both, but who were not selected for obesity (&lt;em&gt;P&lt;/em&gt;=0.00022 versus the cohort selected for obesity).&lt;/p&gt;
&lt;p&gt;Analysis of those with the missing genes revealed an age-dependent link to weight: All four teens and adults were obese. Children were often obese (four of 15) or overweight (two of 15). Children under 2 years all had normal weight.&lt;/p&gt;
&lt;p&gt;So to see whether the deletion was independent of neurodevelopmental problems, Froguel&apos;s group examined genome-wide association study data from general population cohorts totaling 11,856 individuals along with 2,772 from childhood obesity and adult morbid obesity case-control studies, 931 in an extreme early-onset obesity study, and 141 who had bariatric weight-loss surgery.&lt;/p&gt;
&lt;p&gt;All adult carriers of the deletion were obese with the exception of one who was apparently diabetic. Each of the seven children and adolescents who carried the variant had a BMI in the top 0.1% for their age and gender.&lt;/p&gt;
&lt;p&gt;None had any reported developmental or cognitive problems. Four had reported hyperphagia with excessive hunger and food intake.&lt;/p&gt;
&lt;p&gt;Altogether, the 16p11.2 deletions predicted 29.8-fold elevated risk of obesity (&lt;em&gt;P&lt;/em&gt;=0.00000058) and 43.0-fold elevated risk of morbid obesity (&lt;em&gt;P&lt;/em&gt;=0.000000064) compared with lean or normal weight.&lt;/p&gt;
&lt;p&gt;By extrapolation, the researchers extrapolated that about 0.4% of all morbidly obese cases are attributable to an inherited 16p11.2 deletion, with 0.3% arising from a de novo deletion in the same genetic region.&lt;/p&gt;
&lt;p&gt;&quot;Although they may be heterogeneous in nature, these deletions are highly likely to be the causal variants,&quot; they wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by &quot;Le Conseil Regional Nord Pas de Calais/FEDER&quot; along with various governmental and industry supporters for the various component studies.&lt;/p&gt;&lt;p&gt;The researchers reported no financial conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_306"
                     title="In Diabetes, Get Glucose Control &apos;Just Right&apos; (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/Endocrinology/Diabetes/tb/18170?impressionId=1265754969053"
                     
      Intensive treatment to achieve normoglycemia in type 2 diabetes may be almost as bad for survival and heart health as leaving glucose levels elevated, according to a study of real-world practice.&lt;br&gt;
&lt;br&gt;The study turned up a U-shaped link between all-cause mortality and glycosylated hemoglobin levels in which those at a median of 7.5% carried the lowest risk, found Craig J. Currie, PhD, of Cardiff University in Cardiff, Wales, and colleagues.&lt;br&gt;
&lt;br&gt;By comparison, patients who reached normal glycosylated hemoglobin levels with a median of 6.4% were at 52% greater risk of dying from any cause during the study period (95% confidence interval 32% to 76%).&lt;br&gt;
&lt;br&gt;Those in the highest decile with a median of 10.5% hemoglobin A1c were at 79% elevated risk (95% CI 55% to 106%), the researchers reported online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;If confirmed, diabetes guidelines might need revision to include a minimum hemoglobin A1c value,&quot; they wrote in the study.&lt;/p&gt;
&lt;p&gt;Richard Bergenstal, MD, president for medicine and science of the American Diabetes Association, agreed that confirmation would be key and cautioned against overinterpreting the results.&lt;/p&gt;
&lt;p&gt;Practice doesn&apos;t change based on epidemiological evidence alone, particularly when it fits with only part of the clinical trial literature, he noted.&lt;/p&gt;
&lt;p&gt;Among the several recent large clinical trials to examine tight glucose control with hemoglobin A1c goals below the standard 7%, only one showed a negative impact on survival  --  22% excess mortality in the &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; target=&quot;_blank&quot;&gt;ACCORD trial&lt;/a&gt; with an ultra-tight target under 6.0%.&lt;/p&gt;
&lt;p&gt;A &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; target=&quot;_blank&quot;&gt;meta-analysis&lt;/a&gt; of the trials suggested no reduction in all-cause or cardiovascular mortality, stroke, amputations, or even microvascular complications with aggressive glycemic control strategies aiming to bring A1c under 7%.&lt;/p&gt;
&lt;p&gt;Although the reason behind the elevated mortality in ACCORD remains a &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; target=&quot;_blank&quot;&gt;mystery&lt;/a&gt;, &quot;the most plausible explanation for these results is hypoglycemia: the treatment target was probably too low, or glucose lowering was too rapid, or the combinations of treatments led to hypoglycemia,&quot; according to an accompanying editorial in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The new observational data may shed some light on this issue, wrote Beverley Balkau, PhD, and Dominique Simon, MD, PhD, both of the INSERM Center for Research in Epidemiology and Population Health in Villejuif, France.&lt;/p&gt;
&lt;p&gt;Currie&apos;s group retrospectively reviewed data from medical records of British primary care physicians in the U.K. General Practice Research Database from November 1986 to November 2008.&lt;/p&gt;
&lt;p&gt;They identified two cohorts of patients 50 years and older with primary type 2 diabetes: 27,965 whose treatment had been intensified from oral monotherapy to combinations of oral blood-glucose lowering agents, and 20,005 who switched to regimens that included insulin.&lt;/p&gt;
&lt;p&gt;Initial hemoglobin A1c levels were 9.0% and 10.0% in the two groups before intensification of treatment.&lt;/p&gt;
&lt;p&gt;&quot;This two-cohort approach was intended to establish whether any emergent patterns were independent of diabetes treatment regimen,&quot; the researchers explained in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;After an average of 4.5 to 5.2 years of follow-up, patients in the lowest and highest deciles of achieved hemoglobin A1c were at elevated risk of death from any cause in both unadjusted and adjusted analyses.&lt;/p&gt;
&lt;p&gt;In the cohort treated with oral drugs alone, only the highest and lowest deciles, for whom the median hemoglobin levels were 10.5% and 6.4% respectively, were at elevated risk.&lt;/p&gt;
&lt;p&gt;In the group treated with insulin, significantly elevated risk was seen in the three lowest and two highest groups compared with the lowest risk decile (median 7.5% hemoglobin A1c).&lt;/p&gt;
&lt;p&gt;The researchers also found the same U-shaped relationship between glucose control and new-onset, large-vessel cardiac disease events.&lt;/p&gt;
&lt;p&gt;The lowest hemoglobin A1c group was at 54% increased risk for cardiac events (28% to 84%) while the highest decile was at 36% elevated risk (95% CI 14% to 61%) compared with the group who had a median 7.5% hemoglobin A1c.&lt;/p&gt;
&lt;p&gt;One of the risk factors for these hazards appeared to be insulin-based regimens.&lt;/p&gt;
&lt;p&gt;A sensitivity analysis excluding patients with high cardiovascular risk revealed 46% higher mortality risk (95% CI 34% to 59%) with insulin-based therapy than with oral combination therapy.&lt;/p&gt;
&lt;p&gt;Insulin treatment was also associated with 31% elevated likelihood of progression to a first large-vessel disease event (95% CI 22% to 42%).&lt;/p&gt;
&lt;p&gt;Since previous studies have shown greater hypoglycemia risk with insulin treatment than with oral agents, such as sulfonylurea therapy, this result further implicates hypoglycemia in the premature death associated with tight glucose control, Balkau and Simon said.&lt;/p&gt;
&lt;p&gt;&quot;Priority should be given to insulin sensitisers for as long as possible in patients with type 2 diabetes, because these drugs allow a low hemoglobin A1c to be targeted without any risk of hypoglycemia,&quot; they wrote in the editorial.&lt;/p&gt;
&lt;p&gt;However, the researchers noted that another possible explanation is that the insulin-treated patients were older with more comorbidities and longer disease duration.&lt;/p&gt;
&lt;p&gt;They also cautioned that residual sources of confounding were possible, such as different prescribing patterns for cardiovascular prophylaxis across the hemoglobin A1c groups.&lt;/p&gt;
&lt;p&gt;Other limitations of the study included missing data, different timing and methodologies for measuring hemoglobin A1c, and inclusion of patients who could be assigned to both cohorts.&lt;/p&gt;
&lt;p&gt;Overall, these results should be a reminder that the &quot;lower is better&quot; paradigm has given way to individualized treatment targets, Bergenstal concluded.&lt;/p&gt;
&lt;p&gt;&quot;We need to keep trying to understand the data so we get the right patients into the right A1c targets,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by Eli Lilly and Company.&lt;/p&gt;&lt;p&gt;Currie reported conflicts of interest with Astellas, Diabetes UK, the European Association for the Study of Diabetes, the Engineering and Physical Sciences Research Council, Ferring, GSK, Lilly, Medtronic, the Medical Research Council, Pfizer, sanofi-aventis, the National Health Service, Wyeth, Amylin, Aryx, Boeringher Ingelheim, Bristol-Myers Squibb, Eisel, Ferring, Ipsen, Merck, and Takeda.&lt;/p&gt;&lt;p&gt;Several co-authors reported being employed by Eli Lilly and Company. Other co-authors reported financial conflicts of interest with Abbott, Allergan, BMS, GSK, Lilly, Novartis, Novo Nordisk, MSD, Roche, sanofi-aventis, Takeda, Astellas, Ferring, Medtronic, and Wyeth (Pfizer).&lt;/p&gt;&lt;p&gt;Balkau reported having served as a speaker for sanofi-aventis and on advisory panels for AstraZeneca, Bristol Myers Squibb, Lilly, and sanofi-aventis. Simon reported having served as a speaker for GlaxoSmith Kline, sanofi-aventis, Servier, and on advisory panels for AstraZeneca, Bristol Myers Squibb, GlaxoSmith Kline, and Novartis.&lt;/p&gt;&lt;p&gt;Bergenstal reported receiving research funding and serving on advisory boards for various pharmaceutical companies related to novel diabetes treatments but without any related personal compensation.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_280"
                     title="Better Overall Diabetes Care Lowers Nephropathy Risk (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18136?impressionId=1265754969053"
                     
      &lt;p&gt;Simultaneously achieving tight glucose control and other targets in diabetes reduces the risk of kidney complications, researchers found.&lt;/p&gt;
&lt;p&gt;An aggressive multifactorial intervention appeared to delay diabetic nephropathy better when more targets were achieved (&lt;em&gt;P&lt;/em&gt;=0.002 for trend) in a longitudinal study of Chinese patients led by Ming-Chia Hsieh, MD, PhD, of Kaohsiung Medical University Hospital in Kaohsiung, Taiwan.&lt;/p&gt;
&lt;p&gt;The risk of new-onset microalbuminaria dropped 27.1% for those who met the American Diabetes Association-recommended goal of less than 7% glycosylated hemoglobin (&lt;em&gt;P&lt;/em&gt;=0.03), the researchers reported in the Jan. 25 &lt;em&gt;Archives of Internal Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Reaching the systolic blood pressure goal of less than 130 mm Hg reduced this risk 35.5% (&lt;em&gt;P&lt;/em&gt;=0.002). Achieving the HDL cholesterol goal  --  over 50 mg/dL for women and 40 mg/dL for men  --  reduced the risk by 28.5% (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;&quot;The control of microalbuminuria may halt progress to overt nephropathy and reduce occurrence of cardiovascular events in these patients,&quot; Hsieh&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;They suggested that this type of intensive intervention &quot;can be used at the very early stages of diabetic renal disease.&quot;&lt;/p&gt;
&lt;p&gt;Prior studies had suggested that intensive therapy could prevent nephropathy in patients who had already started showing signs of progression.&lt;/p&gt;
&lt;p&gt;So to see if starting earlier would be as effective, Hsieh and colleagues initiated a longitudinal cohort study of 1,290 patients with type 2 diabetes and normoalbuminuria in which participants received intensified treatment to meet ADA-recommended goals on glucose, blood pressure, cholesterol, and triglycerides.&lt;/p&gt;
&lt;p&gt;To this end, patients got the combined efforts of a physician, nurse, and dietitian working together on counseling and patient education to modify behavior.&lt;/p&gt;
&lt;p&gt;By the end of the intervention patients were more likely to have switched from single agent glucose-lowering treatment to insulin plus an oral hypoglycemic agent and to have gone on an antihypertensive (74% versus 48% baseline), statin (58.1% versus 28.0% baseline), and fibrate (14.0% versus 3.0% baseline).&lt;/p&gt;
&lt;p&gt;By the end of the study period, the mean glycosylated hemoglobin was 7.3%, while blood pressure averaged 129.3/74.4 mm Hg. Mean LDL cholesterol was 98.6 mg/dL, triglycerides were at 116.0 mg/dL, and mean HDL cholesterol was 53.6 mg/dL.&lt;/p&gt;
&lt;p&gt;Over the 4.5 years of follow-up, 16.4% of patients developed new-onset microalbuminuria.&lt;/p&gt;
&lt;p&gt;Unlike attainment of HDL cholesterol, glycosylated hemoglobin, and systolic blood pressure goals, reaching those for LDL cholesterol, diastolic blood pressure, and triglycerides appeared to have little impact on kidney function.&lt;/p&gt;
&lt;p&gt;But the more targets patients reached, the less likely they were to develop microalbuminuria (&lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;The majority of participants in the study reached one or two of the treatment targets (71.4%) and 8.1% achieved three.&lt;/p&gt;
&lt;p&gt;Those who did reach two or three of the goals were at significantly lower risk of new-onset microalbuminuria than the 20.5% who didn&apos;t reach any of the goals (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Those who reached one target tended to be at lower risk as well, but the effect was not significant compared with reaching none of the goals (&lt;em&gt;P&lt;/em&gt;=0.35).&lt;/p&gt;
&lt;p&gt;One of the concerns with the tight glucose control goal has been hypoglycemia. In the study, 217 patients had at least one episode. Four cases involved major hypoglycemia, though without clinical morbidity or mortality.&lt;/p&gt;
&lt;p&gt;Overall, 37 patients died from any cause during the study period.&lt;/p&gt;
&lt;p&gt;A &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; target=&quot;_blank&quot;&gt;review&lt;/a&gt; of recent large trials of aggressive glycemic control  --  U.K. Prospective Diabetes Study (UKPDS) and the U.S.-based ACCORD, ADVANCE, and VA Diabetes trials  --  suggested a two- to threefold increased risk of severe hypoglycemia without macrovascular benefits.&lt;/p&gt;
&lt;p&gt;In the recent &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; target=&quot;_blank&quot;&gt;ACCORD&lt;/a&gt; trial, tight glucose control that brought hemoglobin A1c close to 6%, with a target of less than the standard 7.0%, resulted in 22% excess mortality risk.&lt;/p&gt;
&lt;p&gt;The search for a reason behind this risk has yet to turn up a culprit. &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; target=&quot;_blank&quot;&gt;Analyses&lt;/a&gt; have suggested that hypoglycemia isn&apos;t to blame and that the lower A1c levels themselves aren&apos;t a problem.&lt;/p&gt;
&lt;p&gt;In the wake of the negative findings from ACCORD, ADVANCE, and the VA trials, leading diabetologists had suggested that pushing too hard in people who couldn&apos;t reach the targets might have been at fault.&lt;/p&gt;
&lt;p&gt;Rather than a one-size-fits all approach, the ADA guidelines suggest individualizing treatment targets.&lt;/p&gt;
&lt;p&gt;Hsieh&apos;s group acknowledged that &quot;even with close attention, not all our patients could achieve the ADA-recommended goals,&quot; but re-emphasized that for patients who could achieve targets, there were benefits.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that their study was limited by lack of a comparison group, no data on genetic factors, and use of potentially arbitrary treatment target cutoff points.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_235"
                     title="Congenital Anomalies Linked to Mom&apos;s Diabetes (CME/CE)"
                     score="0"
                     href="http://www.medpagetoday.com/OBGYN/Pregnancy/tb/18065?impressionId=1265754969053"
                     
      &lt;p&gt;Pregestational maternal diabetes was associated with an increased risk of a major congenital anomaly, but obesity itself was not, a cross-sectional study found.&lt;/p&gt;
&lt;p&gt;In a multivariable logistic model, the major contributor to a rising rate of congenital anomalies was maternal pregestational diabetes (OR 3.8, 95% CI 2.1 to 6.6), according to Joseph R. Biggio, Jr., MD, and colleagues from the University of Alabama at Birmingham.&lt;/p&gt;
&lt;p&gt;&quot;Because hyperglycemia is a major contributor to developmental malformations, interventions to address obesity and identify women at risk for diabetes and hyperglycemia should be considered in efforts to reduce the occurrence of congenital anomalies,&quot; they wrote in the February issue of &lt;em&gt;Obstetrics &amp;amp; Gynecology.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Maternal obesity has been linked with numerous problems, including preeclampsia, gestational diabetes, fetal and neonatal death, and birth trauma, but scientists have disagreed over whether it also contributes to the risk of fetal malformations, the researchers noted.&lt;/p&gt;
&lt;p&gt;To help settle the issue, Biggio and colleagues used a perinatal database in their university health system that included all women with singletons delivered between 1991 and 2004.&lt;/p&gt;
&lt;p&gt;They divided the cohort into three time periods  --  1991 to 1994, 1995 to 1999, and 2000 to 2004, with a total of 41,902 pregnancies.&lt;/p&gt;
&lt;p&gt;For their primary analysis, they defined maternal obesity as a first prenatal visit weight greater than 200 lb, because during the earlier epochs many women did not have body mass index (BMI) calculated. For their secondary analyses they used BMI greater than 29 kg/m&lt;sup&gt;2&lt;/sup&gt; as the criterion for obesity.&lt;/p&gt;
&lt;p&gt;In each epoch, there were increases in mean maternal weight, mean BMI, the proportion of women weighing more than 200 lb, the proportion with a BMI greater than 29 kg/m&lt;sup&gt;2&lt;/sup&gt;, and the prevalence of pregestational diabetes (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for all).&lt;/p&gt;
&lt;p&gt;Univariable analysis determined that the rate of major anomalies, particularly involving the cardiac and pulmonary systems, also increased during each time period.&lt;/p&gt;
&lt;p&gt;But there was no independent association between congenital anomalies and maternal obesity using either definition, during any of the three time periods or during the study overall.&lt;/p&gt;
&lt;p&gt;Although no direct association was seen between congenital malformations and maternal obesity, the investigators reported that the proportion of anomalies that could be attributed to obesity increased from 0% to 23% during the overall study period.&lt;/p&gt;
&lt;p&gt;The proportion of anomalies that could be attributed to diabetes ranged from 58% to 76%.&lt;/p&gt;
&lt;p&gt;Moreover, for obese women with diabetes the proportion of anomalies attributed to diabetes increased sharply, from 48% in the first epoch to 74% in the third epoch.&lt;/p&gt;
&lt;p&gt;In contrast, for the obstetric population as a whole, the population-attributable risk of congenital malformation related to obesity rose from near zero in the first epoch to 6.1% in the third epoch, while that related to diabetes increased from 3.3% to 9.2%, the investigators reported.&lt;/p&gt;
&lt;p&gt;During the course of the study there was a nearly 15-lb increase in maternal weight and a 30% increase in the proportion of women whose BMI exceeded 29 kg/m&lt;sup&gt;2&lt;/sup&gt;.&lt;/p&gt;
&lt;p&gt;There also was a nearly twofold increase in the rate of major anomalies  --  and a 250% increase in the prevalence of diabetes.&lt;/p&gt;
&lt;p&gt;The authors observed that there has been much interest in the effects of maternal obesity on birth defects.&lt;/p&gt;
&lt;p&gt;Although the pathophysiologic basis for this possible association have not been identified, hypotheses have included increased serum insulin, lower levels of folic acid, chronic hypoxia, and increased inflammatory mediators.&lt;/p&gt;
&lt;p&gt;&quot;Our study provides evidence that the defects may not be due solely to the maternal obesity per se but may be due to undiagnosed diabetes,&quot; the investigators wrote.&lt;/p&gt;
&lt;p&gt;From a public health standpoint, the study findings suggest that efforts to reduce the prevalence of congenital anomalies should be focused less on obesity and aimed more closely at correcting hyperglycemia.&lt;/p&gt;
&lt;p&gt;&quot;If euglycemia could be achieved before pregnancy, or at least embryogenesis and organogenesis, the majority of these anomalies could potentially be avoided,&quot; they observed.&lt;/p&gt;
&lt;p&gt;They also suggested that even women of normal weight, but with other diabetes risk factors, could benefit from closer attention to glycemic control.&lt;/p&gt;
&lt;p&gt;A weakness of the study was the fact that detailed data on glycemic control was not available in the perinatal database, &quot;and therefore we cannot comment on the association between glycemic control and anomaly rates,&quot; the investigators wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported in part by the National Institute of Child Health and Human Development.&lt;/p&gt;&lt;p&gt;The authors did not report any potential conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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