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© 2006 The Authors. 924 Journal compilation © 2006 Diabetes UK. Diabetic Medicine , 23 , 924– 928 Blackwell Publishing Ltd Letters Letters Letters Letters Tolerance loss in diabetics: association with foreign antigen exposure We read with interest the article by Dr Lawlor's group relating milk avoidance to insulin resistance [1]. Cow's milk has also been causally associated with Type 1 diabetes [2]. However, the pathogenic basis of these associations remains unclear. We hypothesize that the possible role of cow dairy in causing/ accentuating the diabetic state could be due to a loss of oral tolerance leading to a burden on the individual's immune defence systems. Data in support of this hypothesis are presented below. Employing an advanced ex vivo lymphocyte response assay (LRA by ELISA/ACT) we identify patient-specific immunore- activity to over 400 antigens in various clinical settings [3]. Recently, in a community-based randomized clinical trial, we identified such reactivities in cohorts of patients with Type 1 ( n = 27) and Type 2 ( n = 26) diabetes. Patients undertook conventional 'best practices' diabetes management alone (control arm, 13 in each cohort) or additionally carried out a novel patient- specific comprehensive care protocol (test arm, 14 Type 1 and 13 Type 2 diabetics): test patients substituted for their reactive antigens and were advised to follow a repair-stimulating diet including nutrient supplementation plans as detailed previously [4]. Biweekly support group meetings were held where qualified nutritionists provided on-going guidance and instruction to implement their plan. Control subjects attended separate support groups in which the nutritionists provided guidance consistent with American Diabetes Association guidelines. Long-term glycemic control was assessed by changes in HbA 1c levels over a 6-month study period. Individual immune reactants were highly variable. More reactivity was seen in Type 1 than in Type 2 diabetics (Fig. 1). The single most common immune reactant was cow dairy (69% of Type 2 and 28% of Type 1 diabetics; P < 0.01). Although reactivity to environmental chemicals and additives was greater, there was no predilection for any single antigen within these groups. This finding is more striking because asymptomatic (healthy) people show no hypersensitivities (they are tolerant and with functional homeostatic mechanisms; unpublished data). Glycemic control improved following the 6-month com- prehensive care protocol. The fall in average HbA 1c levels was significant among Type 2 diabetics (13.3% reduction in test vs. 2.6% in control subjects; P < 0.05). Although values for Type 1 diabetics did not attain statistical significance, the decrease in HbA 1c levels was greater in test (8.7% reduction) compared with control subjects (5.2%). Importantly, six of 14 (42.86%) Type 1 diabetes test subjects had a reduction in HbA 1c levels of ≥ 1.0, while only three of 11 (27.3%) control subjects had this degree of reduction ( P < 0.05). All but three Type 1 diabetes test subjects achieved an HbA 1c level of ≤ 7, thus achieving the ideal situation of glycemic control. In Type 2 diabetes, values remained above 7, suggesting that addi- tional time or more intensive protocols may be required to achieve target values. Mean insulin levels reduced by 18% in test subjects as against 12% in controls in the Type 2 diabetes cohort, supporting the role of oral tolerance in insulin resistance. Test subjects in both cohorts reported fewer hypoglycemic episodes and reduced insulin requirement when compared with controls and with their own prestudy status. Control subjects' improvement may be due to closer monitoring and the effects of support group meetings. The role of oral tolerance and the immunotoxic effects of xenobiotics and anthropogenics in potentiating and maintain- ing the diabetic state has only recently been recognized [5]. Our findings suggest that immune reactivities to foreign anti- gens in diabetics are clinically important and patient specific. Immunoreactant loads may potentiate poor glycemic control and sustain diabetics in a distressed state [6]. The greater associa- tion of milk drinkers with insulin resistance in Dr Lawlor's study is consistent with our finding of much higher immuno- reactivity for cow dairy among Type 2 diabetics. Immune dysregulation through a loss of oral tolerance may be an important mechanism in this regard. Reducing immunological load for the individual while providing nutrient sufficiency and neurohormonal distress reduction improved glycemic control in this study. Improved glycemic control is the goal of modern diabetes management and translates to better long-term outcomes. While larger studies are needed, we submit that com- prehensive care using patient-specific functional technologies in integrated treatment plans is more cost and outcome effec- tive than current conventional diabetes care alone. Figure 1 Comparison of immunoreactants in Type 1 (j) and Type 2 diabetics (h).

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