Diabetes Mellitus Associated with Acute Recurrent and Chronic Pancreatitis

Briefly noted: MD Bellin et al. JPGN 2019; 69: 599-606.

Using the INSPPIRE database with 397 children with either acute recurrent pancreatitis or chronic pancreatitis, the authors examined the frequency of diabetes mellitus (DM).

Key findings:

  •  6% (n=24) had a diagnosis of DM. This is 30-fold higher than the general pediatric population
  • The group with DM was more likely to have elevated triglycerides (OR 5.21) coexisting autoimmune disease (OR 3.94) or pancreatic atrophy (OR 3.64)
  • The group with DM tended to be older with a mean at first diagnosis of acute pancreatitis of 12.9 years compared to 8.7 years in those who did not develop DM

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Frontenac Hotel, Quebec City

Wrongful Conviction: HCV Acquitted of Causing Diabetes & a Word on Ebola

First about Ebola –here’s the Ebola recommendation from the NEJM editors regarding quarantine:

An excerpt:

The governors of a number of states, including New York and New Jersey, recently imposed 21-day quarantines on health care workers returning to the United States from regions of the world where they may have cared for patients with Ebola virus disease. We understand their motivation for this policy — to protect the citizens of their states from contracting this often-fatal illness. This approach, however, is not scientifically based, is unfair and unwise, and will impede essential efforts to stop these awful outbreaks of Ebola disease at their source, which is the only satisfactory goal…We should be honoring, not quarantining, health care workers who put their lives at risk not only to save people suffering from Ebola virus disease in West Africa but also to help achieve source control, bringing the world closer to stopping the spread of this killer epidemic.

Take-home message: Read the entire editorial why quarantine is not the right approach for asymptomatic returning health care workers.

Direct Ebola Risk to Health Care Workers

Direct Ebola Risk to Health Care Workers

Now in followup to yesterday’s post about HCV and diabetes:

Even Perry Mason would have had a difficult time proving hepatitis C virus (HCV) did not cause diabetes until a recent publication (Hepatology 2014; 60: 1139-49, editorial 1121-23).

In this study using population-based data from the U.S. National Health and Nutrition Examination Survey (NHANES) with 15,128 adult participants, the authors show that the prevalence of diabetes and prediabetes did not differ by HCV status.  The authors used standardized definitions for diabetes and prediabetes and adjusted for major confounders.  The authors did note a relationship between elevated alanine aminotransferase (ALT) with diabetes regardless of HCV status.  In their cohort, 56.7% had normal glucose, 32.8% had prediabetes, 3.2% had undiagnosed diabetes, and 7.3% had diagnosed diabetes.  The mean age progressively increased in these groups: 40.8 years, 51.9 years, 58.9 years, and 59.2 years respectively.

Among those with diabetes, 10.5% were HCV RNA-negative and 12.0% were HCV RNA-positive –unadjusted for ALT values; the unadjusted HCV antibody status was nearly identical at 10.5% and 10.2% respectively. After adjustment, the OR for being HCV RNA-positive was 1.06 (P=0.53) with confidence limits of 0.59-1.90.

In examining the evidence, the editorial and the discussion review previous evidence of a significant association between HCV infection, insulin resistance, and diabetes.  The odds ratio for this association (HCV and diabetes) was estimated to be about 1.7.  The problems with this association were the following:

  • Much of the work was reported from tertiary care centers
  • Advanced liver disease (of any type) is a well-established risk factor for type 2 diabetes (T2DM)
  • Many studies may have included patients with nonalcoholic fatty liver disease which is another risk factor for diabetes
  • These studies did not control for ALT values

Bottomline (from editorial): This study “calls one to reconsider the dogma on the role of IR [insulin resistance] in the pathogenesis of HCV infection and its association with T2DM.” If there is an association, it is much smaller than previous estimates.

Related blog post: Treating HCV Helps Diabetics | gutsandgrowth

Diabetes and Hepatitis C –A Bad Combination

Until recently (see next post tomorrow), it has been well-recognized that there is a connection between chronic hepatitis C infection and diabetes mellitus (DM) (related previous post: Treating HCV Helps Diabetics | gutsandgrowth).  More data confirms that the development of diabetes is associated with increased risk of poor outcomes in HCV-infected patients.

  • Hepatology 2014; 60: 807-14
  • Hepatology 2014; 60: 823-31

In the first study, the authors used a nation-wide cohort comprising >99% of the Taiwanese population.  Among a random sample of 1 million enrollees, 6,251 adult chronic HCV patients were identified from 1997-2009.  Among those who developed DM during the study period (not before), after adjustment for confounding variables, diabetes was an independent predictor for cirrhosis (hazard ratio (HR) =2.5, P<0.001) and hepatic decompensation (HR=3.56, P+0.003).

In the second study, the authors identified consecutive chronic HCV-infected patients with cirrhosis who were hospitalized between 2006-2008 (n=348).  At baseline, 40% had DM.  DM was independently associated with development of ascites (P=0.057), renal dysfunction (P=0.004), bacterial infections (P=0.007), and hepatocellular carcinoma (P=0.016).  The authors suggest that improving diabetes control may improve the outcome of cirrhosis.

Take-home message: New-onset diabetes is a marker for progressive liver disease in patients with chronic HCV infection.  Whether diabetes has a causal role in HCV patient deterioration remains unclear.

Also noted, from Healio Gastroenterology, a recent study suggests that sofusbuvir/ledipasvir reduces HCV-related complications, here’s link: Sofusbuvir/ledipasvir Abstract

Treating HCV Helps Diabetics

There is more data confirming that HCV treatment helps diabetic patients (Hepatology 2014; 59: 1293-1302).

Using a large National Health Insurance Research Database with more than 2.2 million Taiwanese residents diagnosed with diabetes, the authors were able to identiy 1411 HCV-treated patients, 1411 untreated patients, and 5644 uninfected/untreated controls.

Key results:

The risk of end-stage renal disease (ESRD), ischemic stroke and acute coronary syndrome (ACS) were all lower in the HCV-treated patients compared to untreated patients and compared to uninfected/untreated controls:

  • 84% reduction in the risk of ESRD
  • 47% reduction in the risk of ischemic stroke
  • 36% reduction in the risk of ACS

Why does HCV treatment reduce these diabetic complications? While the mechanisms have not been fully elucidated, it is “most likely mediated via viral clearance” which subsequently improves insulin resistance.

While this study has several limitations inherent to a study using a database, the design took efforts to minimize bias and confounding.

Celiac disease and less diabetes?

While there is a well-recognized association between Celiac disease and insulin-dependent diabetes mellitus (IDDM), a recent study shows a lower prevalence of non-insulin dependent diabetes mellitus (NIDDM) and metabolic syndrome in patients with celiac disease (Gastroenterol 2013; 144: 912-17).

You-Tube LinkPatients With Celiac Disease Have a Lower Prevalence  – YouTube..Dr. Toufic A. Kabbani discusses his manuscript “Patients WithCeliac Disease Have a Lower Prevalence of Non-Insulin-Dependent Diabetes Mellitus and Metabolic Syndrome.”

A retrospective review of 840 patients with biopsy-confirmed celiac disease were compared with 840 random matched controls.  Controls were matched for age, sex, and ethnicity.  Mean age was 49.4 years.

Key findings:

  • 26 (3.1%) of celiac disease cohort and 81 (9.6%) (p <0.0001) had NIDDM.
  • 3.5% of celiac disease cohort and 12.7% of controls had metabolic syndrome.
  • Though celiac disease patients had lower BMI, these findings were still present after controlling for this variable.
  • Prevalence of NIDDM was strongly associated with age in both groups.  In celiac cohort, NIDDM occurred in 0% (n=343) of those <45, 3.1% in 45-64, and 9.3% in those >65.  In contrast, the control group had NIDDM in 3.5%, 11% and 19.3% respectively.

With regard to pathophysiology, the authors did not think the protection from NIDDM was related to malabsorption.  Evidence of malabsorption was more common in patients with CD and NIDDM than in those without NIDDM.

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Cardiovascular disease for the entire family

This month’s Journal of Pediatrics features an article for the entire family (J Pediatr 2012; 160: 590-7 [editorial pg 539]).  The authors demonstrate that children screened for cholesterol can serve as an index case for the entire family.  During a 26-year prospective followup of 852 pediatric patients (5-19 years old at enrollment) from Cincinnati, the authors assessed relationships of childhood risk factors with parental cardiovascular disease (CVD), type 2 diabetes (T2DM), and high blood pressure (HBP).

  • Pediatric HBP and low HDL cholesterol were predictive of parental CVD ≤age 50
  • Pediatric HBP and high triglycerides were predictive of parental CVD ≤age 60
  • Pediatric high triglycerides and high LDL cholesterol were predictive of parental CVD ≤age 66

The related editorial reviews large studies regarding lipid assessments, including the Bogalusa study with more than 3000 children and the Muscatine study with more than 14,000 children.  In addition, the editorial reviews the recommendations from an expert pediatric panel which suggested screening all children for dyslipidemia between 9 and 11 years. Interestingly, the editorial reviews the fact that screening for cholesterol has not been shown to harm children.  “The evidence is not sufficient to demonstrate any adverse affects.”

Although no harm has been proven, the expert recommendations do not have prospective data demonstrating benefit either.  While it is known that atherosclerotic lesions, including fatty streaks and calcifications, can develop in childhood, it is not known that current treatment strategies will improve long-term outcomes.  This study, however, provides an additional rationale for screening; namely, by identifying children with dyslipidemia, primary care providers can identify parents with cardiovascular disease who are more likely to benefit from urgent intervention.

Additional references:

  • http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof (cholesterol risk calculator)
  • Pediatrics 2011; 128 (suppl 5): S213-56.  Expert panel guidelines for cardiovascular health and risk reduction in children and adolescents.
  • -NEJM 2011; 365: 2078.  Use of statins to lower LDL to 60-70 range halted progression of coronary artery disease.
  • -Pediatrics 2007; 120: e189, e215.  US Preventive Services Task Force:  “the evidence is insufficient to recommend for or against routine screening for lipid disorders” up to age 20.  Consider pediatric drug Rx:
    1. After dietary failure
    2. LDL >190
    3. LDL >160 & FHx of CVD before age 55
    4. triglycerides >250-500 persistently
  • Pediatric Nutrition Handbook AAP Lipid types:type I -increased trig  (rare)
    type IIa -increased chol & LDL
    (most common)
       Homozygous: chol >500
         xanthomas before 10 yrs, vascular dz before age 20
       Heterozygotes with lower chol
    type IIb -elevated trig & chol/LDL
    (3rd most common)
    type III -abnormal LDL density (rare)
    type IV -elevated trig (2nd most common)
         may be increased with diabetes, obesity, inadequate fasting; may need to study parents to establish dx
    type V -increased trig/VLDL (rare)
         exclude nephrotic synd, hypothyroid, diabetes