Deficiency of folate and vitamin B12 increases oxidative stress in chronic pancreatitis patients.

BACKGROUND: Folate and vitamin B12 are involved in metabolic reactions for combating oxidative stress. We measured erythrocyte folate and plasma vitamin B12 and compared these with blood antioxidants - erythrocyte glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and plasma vitamin C - and marker of lipid peroxidation, thiobarbituric acid reactive substance (TBARS), in chronic pancreatitis (CP) patients. METHODS: One hundred and seventy-five CP patients (91 tropical, 84 alcoholic) and 113 healthy controls were recruited. Erythrocyte folate and plasma vitamin B12 were measured using microbiological assay, and antioxidant levels and erythrocyte TBARS by spectrophotometry. RESULTS: Erythrocyte folate and plasma vitamin B12 were significantly lower in CP patients than controls (225.4 ± 9.13 vs. 380.38 ± 17.29 nmol/L, p < 0.001 and 233.23 ± 10.4 vs. 338.84 ± 19.01 pmol/L, p < 0.001), and in diabetic- vs. non-diabetic CP patients. Blood antioxidant levels were significantly lower and TBARS was higher in CP patients as compared to controls. Low folate level correlated with low GSH levels (r = 0.314, p < 0.001). CP patients with low folate and vitamin B12 had low GSH and GPx levels as compared to patients with normal folate and vitamin B12 levels. Low vitamin B12 level was associated with 3.24 (95% CI 1.11-9.46, p < 0.05) fold increased risk of pancreatic insufficiency. Smoking was associated with 9.82 (95% confidence interval [CI] 3.3-29.22, p < 0.05) fold increased risk of having low folate levels. CONCLUSION: Low folate and vitamin B12 levels were associated with increased oxidative stress in CP patients.

Pancreas and Diabetes Mellitus: The Relationship between the Organ and the Disease.

Diabetes mellitus has been a fascinating disease from the dawn of medical history. The first breakthrough in its treatment came in 1922, with the discovery of insulin which was extracted from the pancreas of a dog. Even earlier, a relationship between pancreas and diabetes mellitus had been suspected by medical scientists. However, the study of diabetes mellitus is much more than its relationship with the pancreas. On the other hand the pancreas has been known to be a very reclusive organ that is hidden away from physicians and surgeons for centuries. In recent times, it has become more accessible and has yielded some of its secrets. The relationship between the pancreas and diabetes mellitus is a story full of complexities and surprises. This article attempts to reveal some of the important events and persons in the story and the controversies surrounding them.

Clinical profile of early-onset and late-onset idiopathic chronic pancreatitis in South India.

BACKGROUND AND AIM: Idiopathic chronic pancreatitis (ICP) is the most common form of chronic pancreatitis reported in India. There is paucity of literature on the prevalence and profiles of early- and late-onset forms of ICP in India. MATERIAL AND METHODS: We compared the profile of early- and late-onset ICP in a patient population attending a tertiary care hospital in South India. RESULTS: Pain was the characteristic feature as more than 90 % with both early-onset and late-onset ICP had pain as the most significant symptom. Onset of pain was at age 14.9 ± 7.7 years in early-onset and at 38.1 ± 9.9 in late-onset ICP (p < 0.001). There was considerable delay between onset of pain in early onset as compared to late-onset ICP. Diabetes was seen in 41.4 % in early-onset as compared to 69.1 % in late-onset ICP (p < 0.001). Pancreatic exocrine insufficiency was seen in 34.4 % in early-onset as compared to 53.2 % in late-onset ICP (p < 0.001). Increased prevalence of exocrine insufficiency and diabetes was observed in late-onset as compared to early-onset ICP. Univariate analysis showed that alcohol use, smoking, age, and family history of diabetes were significantly associated with diabetes. Multivariate analysis showed strong associations for diabetes with smoking (odds ratio (OR) = 4.2), calcification (OR = 7.7), as well as family history and age >40 years. CONCLUSIONS: There were differences between early-onset and late-onset ICP in southern Indian patients. Diabetes was strongly associated with smoking and pancreatic calcification.

Diet, nutrient deficiency and chronic pancreatitis.

The aetiopathogenesis of chronic pancreatitis (CP) appears to be multifactorial with interplay of genetic and environmental factors such as alcohol, smoking and diet. Dietary factors in the form of a fat- and protein-rich diet are important cofactors in the aetiopathogenesis of alcoholic pancreatitis. Malnutrition used to be a hallmark in tropical pancreatitis. Presently, it appears that malnutrition is an effect rather than a causative factor for tropical pancreatitis; however, micronutrient deficiency could possibly be implicated in the aetiopathogenesis. The role of dietary toxins such as cassava is no longer considered an important risk factor; however, these patients are at a higher risk for defective detoxification of cyanogens. Decrease in levels of sulphur amino acids (SAAs), folate and zinc have been reported. Oxidative stress and antioxidant depletion are key pathogenetic mechanisms. The role of antioxidants in pain relief is an area of interest. Supplementation of fat-soluble vitamins and micronutrients is a cornerstone in medical management. Folate and zinc supplementation may be beneficial and is a focus of ongoing research. In the future, prophylaxis for CP by a daily micronutrient tablet among high-risk groups in endemic areas could prove to be a potentially important public health measure. However, further studies are required.

Alcoholic chronic pancreatitis and alcoholic liver cirrhosis: differences in alcohol use habits and patterns in Indian subjects.

OBJECTIVES: Alcohol abuse is a risk factor for both liver cirrhosis and chronic pancreatitis. However, less than 15% of heavy drinkers develop these complications. Coexistence of cirrhosis and pancreatitis in the same patient is considered uncommon. We compared drinking patterns and related patient factors in patients with alcoholic liver cirrhosis and alcoholic chronic pancreatitis. METHODS: A prospective evaluation of 307 patients (all men: 188 with alcoholic liver cirrhosis and 119 with alcoholic chronic pancreatitis) was conducted over a 7-year period using a detailed alcohol assessment proforma. Assessment of demographic features, diet, and other habits like tobacco smoking were recorded. RESULTS: Patients with alcoholic liver cirrhosis were older. The mean ± SD age in alcoholic liver cirrhosis was 52.4 ± 9.16 years and 47.1 ± 9.78 years (P < 0.001) in alcoholic chronic pancreatitis. The mean ± SD age when they started drinking was similar in both groups (22.8 ± 5.32 years and 24.3 ± 6.94; P > 0.05). The mean ± SD duration of drinking was higher in the cirrhosis group (29.5 ± 10.25 years) than in the pancreatitis group (21.5 ± 9.61 years) (P < 0.001). Fifty-nine percent of cirrhosis and 75% of pancreatitis were heavy tobacco smokers (P = 0.004). CONCLUSIONS: There are distinct differences in drinking patterns and related patient factors between alcoholic liver cirrhosis and alcoholic chronic pancreatitis, suggesting the need to orient different interventional strategies.

Assessment of cassava toxicity in patients with tropical chronic pancreatitis.

BACKGROUND AND AIM: There have been conflicting reports on the role of cassava ingestion in tropical pancreatitis (TCP). In this study we aimed to estimate cyanogens detoxifying enzyme rhodanese, thiocyanate and sulfur containing amino acids in cassava consumer as well as cassava non-consumer TCP patients and healthy controls and compare the same. METHODS: Eighty-six TCP patients and 90 healthy controls were recruited. Serum rhodanese, thiocyanate, plasma amino acids, urinary inorganic sulfate/creatinine were measured. RESULTS: There was significant reduction in serum rhodanese activity in both cassava consumer- and non-consumer TCP patients as compared to controls but no significant difference between cassava consumer- and non-consumer TCP patients was observed. Serum thiocyanate was significantly lower in cassava consumer TCP patients as compared to cassava consumer controls but not significantly different from cassava non-consumer TCP patients. Plasma methionine, cysteine and urinary inorganic sulfate / creatinine ratio was significantly lower in both cassava consumer and non-consumer TCP patients as compared to controls but were comparable among cassava consumers and non-consumers. CONCLUSIONS: Significant reduction in rhodanese activity with concomitant decrease in sulfur containing amino acids and antioxidants such as glutathione suggests that TCP patients are at higher risk of defective detoxification of cyanogens. However there was no difference between cassava consumers and non-consumers. Low levels of sulfur amino acids may contribute to the development of pancreatitis.

Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transsulfuration and transmethylation pathways.

OBJECTIVES: Homocysteine has been implicated in vascular dysfunction and thrombosis, as well as inflammatory conditions. This study was aimed to find out whether chronic pancreatitis (CP) is associated with hyperhomocysteinemia and derangements of transmethylation and transsulfuration pathways. METHODS: We estimated homocysteine and its metabolites in 45 alcoholic CP patients, 45 tropical CP patients, and 48 healthy controls. RESULTS: Significant increases in plasma total homocysteine and decreases in red blood cell folate, reduced glutathione, plasma methionine, cysteine, and urinary inorganic sulfate/creatinine ratio were observed in both alcoholic and tropical CP patients in comparison with healthy controls. Red blood cell glutathione and plasma cysteine levels were significantly lower in alcoholic than in tropical CP patients. However, plasma vitamin B12 levels were comparable between CP patients and controls. No significant differences in these parameters were observed between diabetic patients and nondiabetic patients. Multivariate regression analysis showed a significant negative correlation between homocysteine and folate (r = -0.415, P = 0.001) and a positive correlation between glutathione and cysteine levels (r = 0.37, P = 0.003). CONCLUSIONS: Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transmethylation and transsulfuration pathways. Low folate levels observed in these patients seem to have a key role in this derangement.