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Cura e prevenzione del Diabete con digiuno e restrizione calorica. 
Prove sperimentali e cliniche:

Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8.5 yr. 

Am J Physiol Endocrinol Metab 2001 Oct;281(4):E757-65
Gresl TA, Colman RJ, Roecker EB, Havighurst TC, Huang Z, Allison DB, Bergman RN, Kemnitz JW. Wisconsin Regional Primate Research Center, Madison 53715, USA. 

Very-low-calorie-diets: is there a place for them in the management of the obese diabetic?
Diabetes Metab 2000 Jun;26 Suppl 3:46-51 
Monnier L; Colette C; Percheron C; Boniface H. 
Service des Maladies Metaboliques, Hopital Lapeyronie, Montpellier. 
It is well-recognized that standard caloric restrictions (1500 kcal/day) are usually poorly effective in achieving weight losses in overweight type 2 diabetic patients. For that reason very-low-calorie-diets (VLCDs) were developed as a mean for initiating or accelerating weight reduction. Short-term  studies indicate that VLCDs result generally in weight losses that are three times greater than those obtained with standard low-calorie-diets. Fasting  blood glucose values are improving in parallel to weight losses and in many patients the improvement in glycemic control is better than that expected from the magnitude of weight losses. However the results are rather disappointing after several months or years of follow-up. For example it has been demonstrated that weight regain can be observed as soon as the patient is shifted to a refeeding or maintenance dietary program at the end of the VLCD period. Long-term results on glycemic control and body weight reduction are generally similar with standard low-calorie-diets and with VLCDs, the final results depending on the magnitude of weight loss whatever the prescribed diet. At short-term the VLCDs can be helpful first for initiating weight losses  and second for sensitizing the patient to the potential benefits of complying to dietary measures.

Aggressive weight reduction treatment in the management of type 2 diabetes. 
Diabetes Metab 1998 Apr;24(2):116-23 
Scheen AJ. Department of Medicine, 
CHU Sart Tilman, Belgium.
Most patients with Type 2 diabetes are significantly overweight, and diet-induced weight loss can provide marked improvement in their glycaemic control. As conventional therapy combining diet and exercise usually has a poor long-term success rate, more aggressive weight reduction programmes have been proposed for the treatment of severely obese diabetic patients, including very-low-calorie diets, anti-obesity drugs and bariatric surgery. Very-low-calorie diets usually have a remarkable short-term effect, and energy restriction and weight reduction are positive factors for the glycaemic control of obese diabetic subjects. However, the long-term efficacy of these methods remains doubtful since weight regain is a common phenomenon. Although anti-obesity (anorectic) drugs may help patients to follow a restricted diet and lose weight, their overall efficacy on body weight and glycaemia is generally modest,  and their long-term safety still questionable. Interestingly, serotoninergic anorectic agents have been shown to improve both the insulin sensitivity and glycaemic control of obese diabetic patients independently of weight loss. Bariatric surgery may be helpful in well-selected patients. The correction  of weight excess after successful gastroplasty fully reverses the abnormalities of insulin secretion, clearance and action on glucose metabolism present  in markedly obese non-diabetic patients, and allows interruption or reduction of insulin therapy and antidiabetic oral agents in most obese diabetic patients. In conclusion, weight loss is a major goal in treating obese patients with Type 2 diabetes, and aggressive weight reduction programmes may be used in selected patients refractory to conventional diet and drug treatment. However, long-term prospective studies are needed for more precise determination of the role of such a strategy in the overall management of obese diabetic patients.

Improved metabolic control after supplemented fasting in overweight type II diabetic patients.
Acta Med Scand. 1984;216(1):67-74.
Vessby B, Boberg M, Karlstrom B, Lithell H, Werner I.
Twenty obese type II diabetes patients were treated in a metabolic ward during 4 weeks with a very low calorie regimen (200 kcal/day). They were given dietary advice and reexamined 3 months after discharge. Mean body weight decreased by 10 kg during fasting, blood glucose was normalized, urinary glucose  disappeared and the K-value at i.v. glucose tolerance test increased. Fasting serum insulin concentrations decreased by 54%. Serum triglycerides (TG) decreased by 65%, serum cholesterol (Chol) by 28% and high density lipoprotein (HDL) Chol by 14%. Three months later, only serum TG remained significantly  decreased (-47%) while HDL Chol was significantly higher than on admission (+11%). Fasting blood glucose remained significantly lower (-25%) with a low urinary glucose excretion. Supplemented fasting appears to be a safe and useful tool in the treatment of obese type II diabetics. It causes, at least during a limited follow-up period, a significant improvement in glucose control and lipoprotein metabolism in spite of a concomitant reduction of the antidiabetic medication.

Very low calorie diet (VLCD): a useful alternative in the treatment of the obese NIDDM patient.
Capstick F, Brooks BA, Burns CM, Zilkens RR, Steinbeck KS, Yue DK., Diabetes Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Diabetes Res Clin Pract. 1997 May;36(2):105-11,
Conventional treatment of obese noninsulin dependent diabetes mellitus (NIDDM) patients is often unsatisfactory. In this study the efficacy of Modifast,  a commercial very low calorie diet (VLCD), was evaluated in a population of obese poorly controlled NIDDM patients. The mechanisms of action of VLCD in these patients were also studied by comparing: (i) Plasma insulin and glucose profiles after a VLCD and an isocaloric mixed meal and (ii) plasma amino  acid levels, both at baseline and after four weeks of VLCD treatment. A total of 14 obese NIDDM patients (M/F 7/7. median body mass index (BMI) 38.7 kg-2,  interquartile range (IQ) 34.7-46.5 kg-2, waist circumference 116 cm, IQ 106-139 cm, insulin treated 7/14) with poor diabetic control (HbA1c 8.6%, IQ 7.8-10%) were studied. Patients were given a VLCD (425 kcal/day) for 12 weeks. At baseline, VLCD and isocaloric meal tests were performed on consecutive mornings. Fasting plasma amino acid levels were also determined at baseline and after 4 weeks of VLCD treatment. Weight, waist circumference, HbA1c, blood pressure, fasting plasma insulin, total cholesterol and triglyceride levels all fell significantly following VLCD treatment. Insulin therapy was able to be  ceased in the seven insulin treated patients. Oral hypoglycaemic agent dosage fell from a median of eight (IQ 6-12) to two (IQ 0-8) tablets per day (P = 0.03) in patients initially on this form of therapy. Insulin secretion was higher after VLCD than isocaloric meal (P = 0.04). Fasting plasma alanine  level fell from 512.0 (IQ 412.0-563.0) to 374.0 (IQ 342-472.0) mumol/l (P = 0.04) following VLCD treatment. In conclusion, the short term use of a VLCD is very effective in rapidly improving glycaemic control and promoting substantial weight loss in obese NIDDM patients. Moreover, a VLCD diet increases insulin secretion and reduces substrate for gluconeogenesis. Thus, VLCD treatment may improve glycaemic control by factors more than caloric restriction alone.

Metabolic and cardiovascular effects of very-low-calorie diet therapy in obese patients with Type 2 diabetes in secondary failure: outcomes after 1 year.
Diabet Med. 2003 Apr;20(4):319-24
Dhindsa P, Scott AR, Donnelly R.
School of Medical & Surgical Sciences, University of Nottingham, and Jenny O'Neil Diabetes Centre, Southern Derbyshire Acute Hospitals, NHS Trust, Derby, 
UK. AIMS: To evaluate the short-term and 1-year outcomes of an intensive very-low-calorie diet (VLCD) on metabolic and cardiovascular variables in obese patients with Type 2 diabetes (T2DM) and symptomatic hyperglycaemia despite combination oral anti-diabetic therapy +/- insulin, and to assess patient acceptability and the feasibility of administering VLCD treatment to this subgroup of patients in a routine practice setting. 
METHODS: Forty obese patients with T2DM (22 M, mean age 52 years, body mass index (BMI) 40 kg/m2, duration of T2DM 6.1 years) and symptomatic hyperglycaemia despite combination oral therapy (n = 26) or insulin + metformin (n = 14) received 8 weeks of VLCD therapy (750 kcal/day) followed by standard diet and exercise advice at 2-3-month intervals up to 1 year. Insulin was discontinued at the start of the VLCD, and anti-diabetic therapy was adjusted individually throughout the study, including (re)commencement of insulin as required. 
RESULTS: Immediate improvements in symptoms and early weight loss reinforced good compliance and patient satisfaction. After 8 weeks of VLCD, body weight and BMI had fallen significantly: 119 +/- 19-107 +/- 18 kg and 40.6-36.6 kg/m2, respectively, with favourable reductions in serum total cholesterol (5.9-4.9 mm), blood pressure (10/6 mmHg) and fructosamine (386 +/- 73-346 +/- 49 microm) (equates to an HbA1c reduction of approximately 1%). Sustained improvements were evident after 1 year, with minimal weight regain, e.g. mean body weight 109 +/- 18 kg and BMI 37 +/- 4 kg/m2. Glycaemic control tended to deteriorate after 1 year. 
CONCLUSIONS: The absence of a control group is a major limitation, but the results indicate that 8 weeks of VLCD treatment may be effective and well tolerated in symptomatic obese patients with T2DM in secondary failure, producing sustained cardiovascular and metabolic improvements after 1 year. VLCD therapy is a treatment option that deserves greater consideration in this difficult-to-treat patient population.

Intermittent feeding and fasting reduces diabetes incidence in BB rats.
Autoimmunity 1999;30(4):243-50 
Pedersen CR; Hagemann I; Bock T; Buschard K. 
Bartholin Instituttet, Kommunehospitalet, Copenhagen, Denmark.
Food intake may be one of several factors which influence the risk of development of insulin 
dependent diabetes mellitus, but the influence of the pattern of food supply has not been studied previously. The aim of the present study was to investigate the effect of intermittent feeding and fasting upon diabetes in BB rats. This study included three groups. Group 1 served as control and included 77 animals, 79% became diabetic. In groups 2 and 3, after weaning, food but not water was withdrawn from the animals: 24 h twice a week in group 2; 24 h every second day in group 3. Group 2 included 40 BB rats, 50% (p < 0.004) became diabetic. Group 3 included 44 BB rats, 52% (p < 0.01) became diabetic. No differences were seen between sexes. Degree of insulitis was not influenced by changed food supply. Regarding blood glucose, no influence was seen among diabetic animals, among non-diabetic animals changed food supply reduced blood glucose values obtained at the end of the study. Intermittent feeding and fasting tended to reduce mean age at the time of iagnosis of diabetes, significance was reached  only in female animals from group 3 compared to group 1. Body weight was obtained weekly. Intermittent feeding and fasting caused a reduced weight gain in  group 2 as well as in group 3 compared to control animals; however, most pronounced in group 3 and also more pronounced among males compared to females. For pre-diabetic and non-diabetic animals comparable influence on body weight was seen. The main conclusion in the study is that intermittent feeding and fasting reduced diabetes incidence.

The effects of three-week fasting diet on blood pressure, lipid profile and glucoregulation in extremely obese patients. 
Srp Arh Celok Lek. 2007 Jul-Aug;135(7-8):440-6
[Article in Serbian]
Beleslin B, Cirić J, Zarković M, Vujović S, Trbojević B, Drezgić M.
INTRODUCTION: Obesity is often accompanied by a number of complications including diabetes mellitus and cardiovascular diseases. Elevated blood pressure and lipids, as well as deterioration of glucoregulation are attributed, as the most significant factors, to development of diabetes mellitus and cardiovascular complications in obese patients. OBJECTIVE: The aim of our study was to evaluate the effects of a fasting diet on blood pressure, lipid profile and glucoregulatory parameters. 
METHOD: We included 110 patients (33 male and 77 female; mean age 35 +/- 1 years, body weight 131.7 +/- 2.6 kg, body mass index 45.4 +/- 0.8 kg/m2) who were hospitalized for three weeks for the treatment of extreme obesity with the fasting diet. At the beginning, during, and at the end of this period, we evaluated changes in blood pressure, lipid profile, as well as parameters of glucoregulation including glycaemia,  insulinaemia, and insulin sensitivity by HOMA. Oral glucose tolerance test (OGTT) was performed in all patients at the beginning and at the end of the  fasting diet. RESULTS: During the fasting diet, the body weight decreased from 131.7 +/- 2.6 kg to 117.7 +/- 2.4 kg (p < 0.001), the body mass index decreased from 45.4 +/- 0.8 kg/m2 to 40.8 +/- 0.8 kg/m2 (p < 0.001), and both systolic and diastolic blood pressure significantly declined (143 +/- 2 vs.  132 +/- 2 mm Hg, p < 0.001; 92 +/- 2 vs. 85 +/- 2 mm Hg, p < 0.001). In addition, the fasting diet produced a significant decrease in total cholesterol,  LDL cholesterol, triglycerides, as well as basal glycaemia and insulinaemia (p < 0.001) Before the fasting diet, OGTT was normal in 76% of patients, whereas 21% of patients showed glucose intolerance, and 4% of patients diabetes mellitus. After the fasting diet, OGTT was normal in 88% of patients, whereas 12% of patients still had signs of glucose intolerance (p < 0.05). In addition, insulin resistance significantly (p < 0.05) increased from 4 +/- 6% to 89 +/- 13% after the fasting diet.
CONCLUSION: The three-week fasting diet in extremely obese patients produced a significant decrease and normalization of blood pressure, decrease in lipids, and improvement in glucoregulation including the increase in insulin sensitivity.

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