**5.4 Physical activity**

38 Type 1 Diabetes – Complications, Pathogenesis, and Alternative Treatments

The recommendation of the DNSG EASD to consume 2-3 servings of oily fish/week and plant sources of n-3 fatty acids (**Table 4**) is consistent with the findings in studies specific for type 1 diabetes. The prospective cohort study of Lee et al. (Lee CC et al. 2010) found that dietary n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) are inversely associated with the degree but not with the incidence of albuminuria in type 1 diabetes. A hypothesis is that n-3 PUFAs decrease urinary AER via anti-inflammatory mechanisms. It decreases lipopolysaccharide-induced nuclear factor-kB (NF-kB ) activation and monocyte chemoattractant protein (MCP)-1 expression in human renal tubular cells (Lee CC et al. 2010). Further prospective studies and randomized controlled trials are needed to confirm

With regards to protein, the DNSG EASD guidelines recommend an intake of 0.8 g/kg normal body weight in patients with type 1 diabetes and established nephropathy. There are no firm recommendations regarding protein intake for type 1 diabetic patients with incipient nephropathy. An intake of 10-20% of total energy is recommended for patients with no evidence of nephropathy (T**able 4**). The recommendation for protein intake is most important for patients with diabetic nephropathy. The guideline of a restricted protein diet which contains 0.8 g/kg normal body weight for type 1 diabetic patients with established nephropathy was demonstrated by previous research. Several randomized controlled trials showed that protein normalization (protein intake of approximately 0.8 g/kg/day, T**able 1**) had a positive significant effect on albuminuria, although no effect on GFR was found (Brouhard BH& LaGrone L 1990; Zeller K et al. 1991; Dullaart RP et al. 1993; Raal FJ et al. 1994; Hansen HP et al. 1999; Hansen HP et al. 2002). Even a relative risk of 0.23 (95% CI: 0.07-0.72) was found for ESRD in patients assigned to a low protein diet compared with patients assigned to a usual protein diet (Hansen HP et al. 2002). A hypothesis is that excessive protein intake causes renal vasodilatation and glomerular excessive perfusion leading to a raised glomerular transcapillary hydraulic pressure gradient ending in proteinuria and glomerular damage, conversely, will prevent kidney damage (Percheron C et al. 1995). So, indeed protein restriction is beneficial for type 1 diabetic patients with established nephropathy. However, we have to mention that although this beneficial effect of a restricted protein intake was found in randomized controlled trials, the sample size of these trials were really small (maximum of 82 people). Furthermore, we have to consider the feasibility of a protein intake of 0.8 g/kg/day. Percheron et al. (Percheron C et al. 1995) showed that even with this intake the compliance is poor. Further studies with a larger sample size are needed to find a cutoff point for protein intake which would still have a

The DNSG EASD guidelines for alcohol for persons with type 1 and type 2 diabetes recommend a moderate use up to 10 g/day for women and up to 20 g/day for men (**Table 4**). In prior studies, moderate alcohol consumers (30-70 g alcohol per week) had a lower risk of diabetic nephropathy (OR=0.36, 95% CI: 0.18-0.71) and diabetic retinopathy (OR=0.60, 95% CI: 0.37-0.99) in patients with type 1 diabetes (Beulens et al. 2008). Alcohol has favourable effects on HDL-cholesterol, inflammation and inhibition of platelet aggregation

positive effect on diabetic nephropathy and its feasibility.

this hypothesis.

**5.3 Protein** 

**Alcohol** 

There are no specific guidelines concerning physical activity for type 1 diabetic patients. The guidelines mentioned in **Table 4** are only for type 2 diabetic patients. However, it was shown that the guidelines for type 2 diabetic patients are also applicable for type 1 diabetic patients. Several randomized controlled trials (**Table 3**) showed that physical activity (endurance sports; on average 2 times a week 60 minutes) improves physical fitness as well as endothelial function in type 1 diabetic patients (Lehmann R et al. 1997; Fuchsjäger-Mayrl G et al. 2002; Seeger JPH et al. 2011). Especially the improvement in endothelial function is important since endothelial dysfunction is an early sign of atherosclerosis, which is often the underlying cause of CVD. Also a positive effect on lipid related cardiovascular risk factors was found in one study (Lehmann R et al. 1997). However, also this conclusion should be interpreted carefully. Although the evidence is gained from randomized controlled trials, the conditions of these trials are really disappointing. They had a maximum sample size of 23 people, and a minimum sample size of only 9 people. The follow-up period was relatively short, up to four months. The studies of Lehman et al. (Lehmann R et al. 1997) and Seeger et al. (Seeger JPH et al. 2011) not even used a control group. Furthermore CVD risk factors were used instead of CVD as endpoint. So the studies are in agreement with the guidelines but more research in better performed randomized controlled trials is needed to confirm this positive effect of physical activity on CVD in type 1 diabetic patients.

#### **6. Conclusion**

A diet high in fiber, low in saturated fat, moderate in protein intake with moderate alcohol consumption as well as physical activity can be recommended for type 1 diabetic patients to prevent complications. Inspite of the lack of large robust prospective studies, using the available evidence, we can conclude that diet as well as lifestyle could play an important role in preventing longterm complications of type 1 diabetes.

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**3** 

Bruno Vergès

*France* 

*Dijon University Hospital* 

**Lipid Disorders in Type 1 Diabetes** 

*Service Endocrinologie, Diabétologie et Maladies Métaboliques* 

Cardiovascular disease is the major cause of death in persons with type 1 diabetes (Libby et al., 2005). Dyslipidemia has been shown to be a significant coronary heart disease risk factor in type 1 diabetes (Soedamah-Muthu et al., 2004; Grauslund et al., 2010). Thus, it seems important to pay attention to lipid abnormalities, in patients with type 1 diabetes, in order to

Patients with type 1 diabetes show lipid disorders, mostly qualitative abnormalities of lipoproteins, which may promote atherogenesis. The pathophysiology of these lipid abnormalities is not totally explained, but hyperglycemia and peripheral hyperinsulinemia, due to the subcutaneous route of insulin administration, are likely to play a role. After a brief review of lipoprotein metabolism and some information on the role of insulin on lipid metabolism, quantitative abnormalities then qualitative abnormalities of lipoproteins, in

Lipoproteins, which transport non-water soluble cholesterol and triglycerides in plasma, are spherical particles composed of a central core of non-polar lipids (cholesterol esters, triglycerides) and a surface monolayer of phospholipids, free cholesterol and apolipoproteins. Lipoproteins are generally classified according to their density as chylomicron, Very Low Density Lipoprotein (VLDL), Intermediate Density Lipoprotein (IDL), Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). An overview

Chylomicrons, the largest lipoprotein particles, are responsible for the transport of dietary triglycerides and cholesterol. Chylomicrons are composed of triglycerides (85-90%), cholesterol esters, phospholipids and apolipoproteins (mainly apoB48 but also apoA-I and apoA-IV). The formation of chylomicrons takes place in the enterocytes, and the process associating the lipid components (triglycerides, cholesterol esters, phospholipids) and the apoB48 is performed by the MTP (Microsomal Tranfer Protein). Chylomicrons are secreted into the lymphatic circulation before entering the bloodstream. In plasma, triglycerides of chylomicrons are hydrolyzed by the lipoprotein lipase leading to the formation of smaller, triglyceride-poorer particles known as chylomicron-remnants. Chylomicron-remnants are

**1. Introduction** 

reduce cardiovascular disease in this population.

**2. Brief review of lipoprotein metabolism** 

of lipoprotein metabolism is shown in Figure 1.

type 1 diabetes, will be discussed.

**2.1 Chylomicrons** 

World Health Organization (WHO). (2008). "Fact sheet N°310 The top 10 causes of death." Retrieved 21 March, 2011, from

http://www.who.int/mediacentre/factsheets/fs310/en/index.html

