Helicobacter pylori Infection and Insulin Requirement Among Children With Type 1 Diabetes Mellitus

DISCUSSION

The subjects enrolled in this study seem to be representative of the patients seen at our Diabetes Clinic in terms of age, gender, race distribution, and HbA_1c levels. The corresponding values for our overall type 1 diabetic population (n = 187) are age: 12.6 ± 4.2 years; gender: 52% female; race: 50% white, 45% black, and 5% other; HbA_1c: 12.8% ± 3.2% for blacks and 11.0% ± 2.3% for whites (S. Chalew, personal communication). Also, their reported income is in accordance with the median for the state of Louisiana, and the sociodemographic factors that we found associated with H pylori infection (ie, increasing age, poor socioeconomic class, and race [black]) are well recognized.^{7 ,14}

H pylori infection was determined using a serologic test with a reported sensitivity and specificity of 98% and 94%, respectively.¹⁵ Because the validity of commercially available serologic kits in children has been questioned by some researchers,¹⁶ we confirmed the positive results with the urea breath test which, in children, has shown a sensitivity and specificity of 100% and 98%, respectively, compared with histology.¹⁷ The prevalence of H pyloriinfection found in our study (17.2% among children 6–18 years of age) is similar to previously reported values for nondiabetic US children of comparable age (24.1%).¹⁴ Some authors have suggested an increased prevalence of H pylori infection among diabetic patients;¹⁸ however, the validity of those findings has been severely criticized¹⁹ and our results do not support such a notion. Attention should be drawn to the infection rate among the different race groups. All our infected patients were black. The infection rate we found among 6- to 18-year-old blacks was 37.9%, similar to the 40.1% previously described in a population-based study in the US.¹⁴ The same study also reported an infection rate of 17.0% among white children; yet, none of our white patients were found to be infected, although some of them presented the sociodemographic risk factors mentioned above. We have no explanation for this discrepancy at this point, and we are conducting additional seroprevalence studies to clarify this issue.

The primary findings of our study are the increased IU/kg/d requirement and the increased level of HbA_1c among the infected subjects. These two factors are not independent because an elevated HbA_1c level would lead to an increase in the dose of insulin. However, the association between IU/kg/d and H pylori infection remained significant even after controlling for the HbA_1c level (as well as many other possible confounding variables) suggesting that infected children required higher doses of insulin than uninfected children did to achieve comparable levels of HbA_1c. In addition, because all our infected patients were black and diabetes mellitus is known to behave differently in that racial group compared with others, we repeated the analyses including only black patients (infected vs uninfected subjects) and found again that H pylori infection was associated independently with increased IU/kg/d requirement. The regression coefficients obtained by either set of analyses did not vary markedly, again implying an independent effect. The regression coefficients were consistent with an increase of ∼.33 ± .12 IU/kg/d in the insulin requirement among infected children. The clinical relevance of this increased insulin requirement is not directly evident from our cohort, but specially coupled with the elevated HbA_1c levels (∼3% higher among infected subjects), it would suggest a less optimal control of the glycemia that in turn has been associated with the development and progression of long-term complications of diabetes.²⁰ In that particular study, patients on conventional insulin therapy had a HbA_1c level on average 2% higher than those on intensive insulin therapy and developed significantly more retinopathy, nephropathy, and neuropathy.

Although the analyses of our data document the presence of an association between H pylori infection and increased IU/kg/d, interpretation of our results should be cautious. First, similar studies need to be repeated in other populations to ensure that the findings are related to the presence of the infection itself and are not a peculiarity of the H pylori-infected subjects in our community (eg, due to particular dietary or living habits). Second, the observational nature of the study does not allow an evaluation of causality or, for that matter, its direction. In other words, does the presence of the infection affect negatively the control of diabetes, or does the poor control of diabetes favor acquisition of the infection? Or, do unidentified variables lead to both infection and poor control of diabetes? Although all these scenarios are possible, we explained above the biologic plausibility that the presence of H pylori infection could induce chronic inflammation and production of cytokines, leading to impaired secretion of insulin, increased anti-insulin activity, and altered carbohydrate metabolism, all these effects translating into decreased glycemia control.^{4 ,5}

We must acknowledge difficulty in evaluating two of the study variables: income and compliance. Income was measured by self-report and only 73% of families provided the information; therefore, we do not know if any bias could have been introduced. Compliance with the treatment regimen is an important factor for the glycemia control of diabetic patients. Unfortunately, we could not measure compliance with insulin dose administration directly and we used compliance with clinical appointments instead. This surrogate marker did seem to correlate as expected with the other variables (data not shown); however, because it is not a direct measure, we have no way to quantify how much, if any, bias may have been introduced.