**Diet, Lifestyle and Chronic Complications in Type 1 Diabetic Patients**

S. S. Soedamah-Muthu1, S. Abbring1 and M. Toeller2 *1Division of Human Nutrition, Wageningen University, Wageningen 2Department of Endocrinology, Diabetology and Rheumatology Heinrich-Heine-University Duesseldorf 1Netherlands 2Germany* 

### **1. Introduction**

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

Zhou, G., Li C. & Cai, L. (2004). Advanced glycation end-products induce connective tissue

(December 2004), pp. 2033-2043, ISSN 0002-9440

growth factor-mediated renal fibrosis predominantly through transforming growth factor β-independent pathway. *American Journal of Pathology*, Vol.165, No.6,

> Diabetes mellitus is with 220.000 deaths per year the eighth leading cause of death in high income countries (World Health Organization (WHO) 2008)**.** In 2007, over 740.000 people in the Netherlands were suffering from diabetes and this number is expected to grow to 1.3 million people in 2025 (National Institute for Public Health and the Environment (RIVM) 2010). Worldwide approximately 285 million people had the disease in 2010 and this number will increase till 438 million in 2030 (World Diabetes Foundation (WDF) 2010). In 2000, diabetes was most prevalent in India with 31.7 million cases. China (20.8 million cases) and the United States (17.7 million cases) were on the second and third place. Diabetes also has a great economic impact on the individual, nation healthcare system and economy (International Diabetes Federation (IDF) 2010).

> Type 1 diabetes accounts for 5% of all cases of diabetes worldwide. Of this 5% the vast majority are children. In type 1 diabetes the body does not produce insulin (American Diabetes Association (ADA) 2010).The disease has a strong genetic component, inherited mainly through the HLA complex but the exact cause is unknown. Most likely there is an environmental trigger in genetically susceptible people that causes an immune reaction. The body's white blood cells mistakenly attack the insulin-producing pancreatic β-cells (U.S. National Library of Medicine 2011). Putative environmental triggers include viruses (e.g. enteroviruses), environmental toxins (e.g. nitrosamines) or foods (e.g. early exposure to cow's milk proteins, cereals or gluten) (Daneman D 2006). This 'food' trigger explains why type 1 diabetes is less common in people who were breastfed and in those who first ate solid foods at later ages (Sadauskaitė-Kuehne V et al. 2004; American Diabetes Association (ADA) 2010).

> People with type 1 diabetes also have an increased risk of developing some serious and life threatening complications. This involves acute complications, like hyperglycaemia and hypoglycaemia which can lead to a coma, but also chronic complications (National Institute for Public Health and the Environment (RIVM) 2007). Chronic complications can be subdivided into macrovascular and microvascular complications. Cardiovascular disease is the major macrovascular complication and includes mainly myocardial infarction and stroke (American Diabetes Association (ADA) 2010). The risk for cardiovascular disease, is 4-8

Diet, Lifestyle and Chronic Complications in Type 1 Diabetic Patients 23

In the following paragraphs of this bookchapter the literature on associations between diet (including alcohol) and lifestyle and chronic complications in type 1 diabetic patients will be summarized. Since 'diet' and 'lifestyle' are broad terms the focus will be on macronutrients (carbohydrates (including fiber), proteins and fats (including cholesterol), alcohol, physical activity and dietary patterns. The paragraphs are divided by nephropathy, retinopathy and CVD. In the final paragraphs all recommendations on diet and lifestyle in patients with type

Eighteen studies reported an association between macronutrients and type 1 diabetic nephropathy. Of these, thirteen reported results for the association between protein and nephropathy. The other five focussed on other dietary macronutrients such as fat, cholesterol or carbohydrate in relation with nephropathy. There were also three studies that reported results for protein as well as carbohydrate or fats and nephropathy. Furthermore one study reported an association between alcohol consumption and nephropathy in type 1 diabetic patients and one study reported an association between physical activity and nephropathy in type 1 diabetic patients. No studies were found examining the effect of

Of the thirteen studies that reported an association between protein and nephropathy there were three cross-sectional studies (Toeller M et al. 1997; Riley MD& Dwyer T 1998; O'Hayon BE et al. 2000), one case control study (Möllsten AV et al. 2001), two cohort studies (Jibani MM et al. 1991; Barsotti G et al. 1998), six randomized controlled trials (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) and a pilot study (Percheron C et al. 1995). These will be

The three cross-sectional studies were not consistent in their conclusions on the effect of protein on diabetic nephropathy. O'Hayon et al. (O'Hayon BE et al. 2000) failed to show a significant relationship between dietary protein intake and markers of early nephropathy, other than creatinine clearance. Toeller et al. (Toeller M et al. 1997) found a significant relationship between dietary protein intake and urinary albumin excretion rate (AER). A higher AER was particularly found in people consuming more than 20% of their dietary food energy as protein. Riley et al. (Riley MD& Dwyer T 1998) even found the opposite, a

In the case-control study (Möllsten AV et al. 2001) total protein intake was not associated with the presence of microalbuminuria, but a diet including a high amount of fish protein seemed to decrease the risk. Furthermore they could not confirm an association between a high total animal protein intake and having microalbuminuria. In contrast to this finding , Jibani et al. (Jibani MM et al. 1991) found in their cohort study that a predominantly vegetarian diet (low in animal protein) may have an important beneficial effect on diabetic nephropathy without the need for a heavily restricted total protein intake. But they were not able to determine if the reduction in total protein intake rather than the reduction in the fraction of animal origin was primarily responsible for the fall in the fractional albumin clearance. Another (Barsotti G et al. 1998) cohort study showed that a low protein diet has a

glycaemic index/glycaemic load on nephropathy in type 1 diabetic patients.

decreased prevalence of microalbuminuria at high relative intakes of protein.

protective effect on the residual renal function in type 1 diabetic patients.

discussed in the following paragraphs by study design.

1 diabetes will be put in perspective with the current literature.

**2. Diet, lifestyle and nephropathy** 

**2.1 Macronutrients 2.1.1 Protein** 

times higher for people with type 1 diabetes (Soedamah-Muthu SS et al. 2006). The major microvascular complications are diabetic nephropathy, diabetic neuropathy and diabetic retinopathy (American Diabetes Association (ADA) 2010). Of the patients with type 1 diabetes approximately 29% develop persistent microalbuminuria (urinary albumin excretion rate between 30 and 300 mg/24 h) after 20 years. Of these 29%, 34% progressed further to persistent macroalbuminuria (urinary albumin excretion rate > 300 mg/24 h). Persistent microalbuminuria is a risk factor for the development of diabetic nephropathy. Microalbuminuria can be seen as an early marker of diabetic kidney disease (Hovind P 2004). Also retinopathy is a common microvascular complication. The 25-year cumulative incidences of any visual impairment and severe visual impairment are 13% and 3%, respectively. Diabetic retinopathy is an important cause of visual impairment (Klein R et al. 2010). Finally the high incidence of lower extremity amputations also stresses how serious the complications of type 1 diabetes are. The overall 25-year incidence of lower extremity amputations is 10.1% in 943 American type 1 diabetic patients (Sahakyan K et al. 2011). These complications account for the major morbidity and mortality associated with type 1 diabetes, so it is very important to treat them (Daneman D 2006).

In type 1 diabetes, special attention is paid to balancing the insulin dose with episodes of activity and the quantity and timing of food intake to prevent acute episodes of hypoglycaemia and hyperglycaemia (Franz MJ et al. 2003). This is important because these acute complications can lead to a coma, but also because a high blood glucose concentration (glycosylated hemoglobin (HbA1c) ≥ 7%) in people with diabetes increases the risk for macrovascular as well as microvascular complications. Other risk factors for these chronic complications are smoking, obesity, physical inactivity, high blood pressure and high cholesterol levels. Also people with a longer history of diabetes have a higher risk (National Institute for Public Health and the Environment (RIVM) 2007). Furthermore it is important to realise that the microvascular complications lie on the pathway between diabetes and cardiovascular disease. Nephropathy for example is an important risk factor for cardiovascular disease in people with type 1 diabetes (Jensen T et al. 1987).

Recent studies have shown that people with type 1 diabetes eat a more atherosclerosisprone diet. This includes a high intake of energy from saturated fat and a low intake of fiber, fruits and vegetables, which could increase the risk of the development of atherosclerosis. An atherogenic diet may contribute to the risk of cardiovascular disease (Øverby NC et al. 2006; Snell-Bergeon JK et al. 2009). It has been demonstrated that 80%-90% of type 2 diabetes and coronary heart disease cases can be prevented by healthy lifestyle behavior with a focus on healthy diet and exercise.(Stampfer et al. 2000; Hu et al. 2001; Yusuf et al. 2004) These studies suggest that there could be a potential role for diet in type 1 diabetes to reduce the risk of cardiovascular disease.

There are more studies suggesting that diet (including alcohol) can play an important role in treating the complications of diabetes (Franz MJ et al. 2003; Franz et al. 2010). Several studies have reviewed nutritional recommendations for people with diabetes (Franz MJ et al. 2003; Toeller M July 2010). But most of these recommendations combine both type 1 as well as type 2 diabetes. Furthermore they are general and not always specific for the different type of complications. An overview of the relationship between diet (including alcohol) and complications in type 1 diabetic patients is lacking. Also the effect of lifestyle (including physical activity and dietary patterns) on complications is still not elucidated for type 1 diabetic patients. Lack of physical activity together with an atherogenic diet could enhance development of complications especially in high risk type 1 diabetic patients.

In the following paragraphs of this bookchapter the literature on associations between diet (including alcohol) and lifestyle and chronic complications in type 1 diabetic patients will be summarized. Since 'diet' and 'lifestyle' are broad terms the focus will be on macronutrients (carbohydrates (including fiber), proteins and fats (including cholesterol), alcohol, physical activity and dietary patterns. The paragraphs are divided by nephropathy, retinopathy and CVD. In the final paragraphs all recommendations on diet and lifestyle in patients with type 1 diabetes will be put in perspective with the current literature.
