How many people in Germany are affected by diabetes?

Currently, at least 8.7 million people in Germany have type 2 diabetes and 32.000 children and young people and 340.000 adults have type 1 diabetes. Through measures to combat pandemics (e.g. a. Lockdowns) in 2020/2021 are assuming a significantly increased risk of diabetes in the population, especially.a through reduced physical activity and weight gain. (Source: https://www.diabetesde.org/system/files/documents/gesundheitsbericht_2023_final.pdf)

 

What exactly is meant by diabetes mellitus?

After eating food rich in carbohydrates, the blood sugar level rises, whereupon more insulin is released. Insulin stimulates fat, liver and muscle cells to absorb glucose from the blood, which lowers blood sugar levels again.

Diabetes mellitus is the umbrella term for metabolic diseases due to elevated blood sugar levels, which result from an absolute lack or reduced effect of the hormone insulin (relative deficiency). Due to the lack of insulin, the glucose can no longer be absorbed into the cells and therefore no longer be used there as an energy source. Instead, glucose builds up in the blood.

From a certain concentration onwards, more glucose is excreted via the kidneys/urine and there is a loss of water and electrolytes.

 

What is the difference between type 1 and type 2 diabetes?

If there is absolute insulin deficiency (IDDM) it is called type 1 diabetes, if it is relative Insulin deficiency or Insulin resistance is called Type 2 Diabetes (NIDDM), i.e.H The target tissues primarily respond inadequately to insulin secreted.

Type 1 diabetes

• Absolute insulin deficiency, as not enough insulin is produced in the pancreas
• It is an autoimmune disease in which the body's own immune system destroys the insulin-producing β cells in the pancreas.
• Starts i.dR already in childhood/adolescence
• There is currently no cure, so insulin must be injected for life

Type 2 diabetes

• Is caused by reduced sensitivity of the body's cells to insulin (insulin resistance) and by "exhaustion" of the insulin-producing cells in the pancreas due to years of overproduction of insulin
• Starts i.dR creeping and occurred earlier v.a occurs in old age (“adult-onset diabetes”), but now increasingly also in young adults and adolescents
• In addition to genetic disposition v.a The following risk factors: lack of exercise, overweight, unbalanced diet (low in fiber and high in fat and sugar) and smoking

The consequence of both forms of diabetes is a glucose deficiency in target tissues and an excess of glucose in the blood.

 

 

What accompanying and secondary diseases occur with diabetes mellitus?

The diabetes health report provides an overview of the frequency of occurrence of accompanying and secondary diseases at 120.000 type 2 diabetics cared for:

• 75.2% hypertension
• 11.9% diabetic retinopathy
• 10.6% neuropathy
• 9.1% heart attack
• 7.4% peripheral arterial disease (PAD)
• 4.7% stroke
• 3.3% nephropathy (kidney insufficiency)
• 1.7% diabetic foot syndrome
• 0.8% amputation
• 0.3% blindness

 

Oxidative stress as a central cause of many sequelae/accompanying diseases of diabetes mellitus

All available parameters that are considered an indirect measure of oxidative stress (direct measurement is not possible in vivo) are increased in diabetic patients. Therefore, the formation of free radicals as a consequence of oxidative stress is now viewed as the central biochemical explanation for diabetes-associated diseases (cf. David et al., Ceriello et al.)

Increased glucose concentrations in the blood lead to a reaction of sugars with the body's own proteins - this is called glycosylation and the result is so-called AGEs ("Advanced Glycation Endproducts" - these are cross-linked structural proteins), which the immune system subsequently tries to break down. Immune cells such as Macrophages have receptors that recognize these AGEs (so-called “RAGE”). The glucose-induced increase in AGE in the blood increases the production of these receptors and leads to a macrophage-induced immune reaction and chronic inflammation, which in turn leads to oxidative stress and thus the development of vascular damage.

The majority of diabetes-associated diseases arise from pathological changes in smaller areas (microangiopathy --> etc.a retinopathy, nephropathy, neuropathy) and larger ones (macroangiopathy --> v.a atherosclerosis) blood vessels. Free radicals not only damage cellular membranes, but also lead to changes in the structure and function of the affected vascular cells.

The oxidative phosphorylation that occurs in the “power plants of our cells”, the mitochondria, is also accompanied by the formation of oxygen radicals. If there is an excess supply of glucose, free radicals are increasingly formed due to a dysregulation of mitochondrial metabolic processes. On the other hand, antioxidant protective enzymes are increasingly glycosylated and their function is therefore impaired.

Brownlee and colleagues have succeeded in demonstrating that overloading vascular cells with substrates such as glucose (hyperglycemia) and fatty acids (hyperlipidemia) impairs mitochondrial electron flow (in the electron transport or respiratory chain) increases to such an extent that massive formation of free radicals occurs. In their studies, they were able to demonstrate both the dependence of radical formation on the substrate supply and the partial uncoupling of the mitochondrial electron flow between complexes II and III of the respiratory chain. At the same time, they were able to show that diabetes-specific signaling pathways that lead to vascular complications are activated as a result of mitochondrial radical formation. These include activation of protein kinase C, the hexosamine metabolic pathway, transcription factors NFκB and SP-1, and reduced availability of nitric oxide (NO).

Oxidative stress also increases insulin resistance

Free radicals as a result of oxidative stress and their cytotoxic effects also contribute to the destruction of β-cells in the pancreas through apoptosis, so that the synthesis of insulin is further impaired and insulin deficiency occurs. This is, for example, Insulin-dependent uptake of glucose by adipocytes and L6 muscle cells is disrupted when these cells are exposed to oxidative stress.

This results in an increasing system of insulin deficiency and oxidative stress.

Additionally, diabetes contributes – especiallya in a large number of older patients - a reduced antioxidant capacity contributes to the increase of oxidative stress, as the supply of antioxidants such as vitamin C, E, coenzyme Q10 or polyphenols such as quercetin, resveratrol, OPC etc. is often inadequate, especially in old age.

If the oxidative stress is regulated using antioxidants, the insulin-dependent glucose uptake by the cells is normalized again (cf. Klip et al).

 

What are the typical risk factors for the development of diabetes mellitus?

 

“Classic” risk factors:

• Metabolic syndrome
  • Fat metabolism disorder
  • Hypertension
  • Overweight/body fat distribution
• Unfavorable diet (--> oxidative stress)
• Lack of exercise (--> oxidative stress)
• Smoking (--> oxidative stress)

 --> Domain of “lifestyle medicine”

Risk factors that can be influenced by micronutrients:

• (chronic) inflammation (“silent inflammation”)
• Hyperhomocysteinemia
• Nitrogen imbalance, ADMA elevation and relative arginine deficiency
• Disorders of mitochondrial function
• Increase in Lp(a), fibrinogen and plasmin activator
• Disturbance of erythrocyte and platelet function
• Stress, depression etc.a psychogenic stress
• Oxidative stress = disproportion (radicals – antioxidants)

 --> Domain of orthomolecular medicine

 

 

Evidence-based therapeutic basic measures of “lifestyle medicine”

• 8 weeks of medically supervised nutrition with only 600 kcal (only non-starchy vegetables and diet drinks) à 7 out of 11 patients with type 2 diabetes for years (insulin production and liver function are normalized) are cured of her illness. In addition, it has long been known that every second Patient who loses 10 kg soon after diagnosing diabetes and gets well again.
  (Sources: Lim EL et al.; Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol; Diabetologia 2011; doi: 10.1007/s00125-011-2204-7; SZ 1.72011
• High sugar consumption promotes obesity, type 2 diabetes, dyslipidemia, hypertension and cardiovascular diseases (sources: prospective study at 11.733 adults; JAMA Intern Med. 2014 Apr;174(4):516-24. doi: 10.1001/jamainternmed.2013.13563. Added sugar intake and cardiovascular diseases mortality among US adults. Yang Q1, Zhang Z1, Gregg EW2, Flanders WD3, Merritt R1, Hu FB4.)
• A "Mediterranean" diet is favorable with a high proportion of fiber-rich fruits, vegetables, legumes, little red meat, more fish, more monounsaturated fats such as olive oil.
• “Diabetics must be informed about the targeted supplementation of vital substances to prevent diabetic complications – vision loss, amputations, strokes and heart attacks.“
  (Source: Prof. HP Meissner, diabetologist, Berlin, ÄP 4.102002)
• The American Diabetes Association has officially recommended low-carb as an option for diabetes therapy since 2020: “.Reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia and may be applied in a variety of eating patterns that meet individual needs and preferences. For individuals with type 2 diabetes not meeting glycemic targets or for whom reducing glucose-lowering drugs is a priority, reducing overall carbohydrate intake with a low- or very-low-carbohydrate eating pattern is a viable option..." (Source: https://care.diabetesjournals.org/content/43/Supplement_1/S48.full-text.pdf)

 

 

 

Which micronutrients/food supplements are relevant for diabetes mellitus?

 

Vitamin C

• Vitamin C inhibits the enzyme aldose reductase (AR) and thus sorbitol formation (aldose reductase is an enzyme that converts glucose to sorbitol). Because in diabetes mellitus, the AR produces a lot of sorbitol, which accumulates in the cells and especially.a In kidneys, eyes and nerves damage caused by the high osmotic pressure.
• Inhibits protein glycosylation (displaces glucose from protein binding sites) and thus the formation of AGE (with the above.G negative effects). With vitamin C deficiency, the glycosylation rate is increased!
• Most important water-soluble antioxidant
  • Reduces free radicals resulting from oxidative stress
  • Protects folic acid & vitamin E from oxidation
• Important for synthesis of carnitine, neurotransmitters & collagen
• Lowers insulin resistance and HbA1c (indicator of blood sugar over the last 2-3 months, as it shows the proportion of red blood pigment to which sugar is bound). This is because vitamin C intake increases the concentration of reduced glutathione in the plasma, which causes a change in membrane permeability. This results in improved insulin effectiveness, which enables increased transport of glucose into the cell.
• Lowers LDL cholesterol: The decrease in LDL cholesterol can be explained by the fact that vitamin C, with its antioxidant effect, protects LDL cholesterol from non-enzymatic glycosylation and peroxidation, so that it can be dismantled unhindered. The concentration of HDL cholesterol, the so-called “good” cholesterol remains unaffected by increased vitamin C intake.
• Improves (endothelium-dependent) vasodilation (= expansion of the blood vessels and thus improvement of blood circulation)

Diabetes patients have i.dR Vitamin C deficiency:

• Diabetes patients have at least 30% lower Vit C levels (Nutr Rev 1996; 57; 193-202)
• HbA1c and Vit C levels correlate inversely (Diab Care 2000; 23; 726-732)

Causes of vitamin C deficiency in diabetes

• Increased vitamin C requirement due to oxidative stress
• Hyperglycemia inhibits active vitamin C absorption
• Diabetics have approx. 50% reduced storage capacity for vitamin C

Typical dosage: 500-2000 mg (divided into multiple servings) over 4 months; The aim is to have a mirror like that of healthy people; Diabetics need ~twice as much vitamin C! à “In order to be able to determine the positive effects of vitamin C described in the studies, a vitamin C intake of 500 to 1000 mg per day is necessary. When taking a high-dose vitamin C preparation, pay attention to its bioavailability. With conventional preparations, only a small part of the amount of vitamin C absorbed is actually available to the body, since, on the one hand, the absorption rate decreases as the dosage increases and, on the other hand, if the vitamin C blood level rises too quickly and too high, part of it increases is disposed of in the urine.“
(cf. https://www.deutsche-apotheker-zeitung.de/daz-az/1997/daz-42-1997/uid-2313)

 

Vitamin E

• Most important fat-soluble antioxidant
• Inhibits oxidation of lipids, enzymes & hormones (increased lipid peroxidation in diabetics
  due to increased glycosylation of plasma proteins)
• Reduces platelet adhesion & aggregation: Mayne et al. (1970) and Jäger et al. (1975) demonstrated significantly higher platelet stickiness in diabetics compared to normal individuals.
• Reduces protein glycolysis and thus AGE formation
• Decreases thromboxane synthesis (thromboxane activates platelet aggregation)
• Improves the effect of insulin (reduces insulin requirement)
• Reduces risk of retinopathy and nephropathy
• Reduces fatal heart attacks by 77% (source: Chaos study 1996)
• Vitamin E requirement increased in diabetes
• Low vitamin E levels increase the risk of diabetes 4-fold
• Typical dosage: 100-600 mg per day

 

B vitamins

Possible causes of B vitamin deficiency in diabetes:

• Insufficient intake, wrong diet, high consumption
• Increased excretion in the urine (glucosuria)
• Chronic illnesses, medication, if applicable. increased alcohol consumption

Relevance of B vitamins in connection with diabetes:

• Water-soluble coenzymes in carbohydrate, amino acid and fat metabolism (B1, B2, B3, B5, B6, folic acid)
• Antioxidant effect (B2, B3)
• Important for nerve metabolism (“neurotropic”): improvement in pain and nerve conduction speed (B1, B6, B12)
• Regeneration of B cells, formation of glucose tolerance factor (B3)à mediates binding of the
  insulin to the insulin receptor
• Inhibition of glycolation, improvement of glucose tolerance (B1, B6)
• Homocysteine ​​reduction (B6, B12, folic acid)
• Cofactors for energy production in the mitochondria (B1, B2, B3, B5)
• DNA synthesis (B12)
  (Sources: Arzneimittel-forschung 1990; 49, 220-224; Exp Clin Endocrinol Diabetes 1996; 104; 311-316)

Typical Dosage: preferably a high-dose B complex, as B vitamins activate each other

 

 

Zinc

Possible causes of zinc deficiency in diabetes:

• Increased zinc excretion via urine (2-3x more)
• Low zinc intake (e.g.b with a one-sided diet, reduction diet)
• Decreased absorption in pancreatic insufficiency, malabsorption, high-fiber diet (zinc-phytate complexes)

 

Relevance of zinc in connection with diabetes: Reduces NBZ & HbA1c & insulin requirements

• Important for insulin production in alpha and beta cells of the pancreas; stabilizes the structure of crystalline insulin (insulin storage in the form of a zinc-insulin complex)
• Increases the ability to bind to the insulin receptor
• Influences the enzyme carboxypeptidase B (catalyzes the conversion of proinsulin into insulin)
• Stimulates glucose metabolism in the muscles
• Promotes cellular glucose transport & glucose utilization
• Improves glucose tolerance & insulin sensitivity
• Zinc, along with copper and manganese, is a component of superoxide dismutase (SOD) - an enzyme important for the deactivation of free oxygen radicals
• Promotion of humoral & cellular immune defense
• Reduction of wound healing disorders in diabetes

Typical Dosage: 10-25 mg/day - initially also up to 3 x 25 mg/day

 

Magnesium

• Improves insulin sensitivity and reduces insulin resistance
• Use before the onset of diabetes (in case of insulin resistance)
• Controls tyrosine kinase on the insulin receptor à Tyrosine kinases are a group of enzymes from the protein kinase family whose task is the reversible transfer of a phosphate group (phosphorylation) to the hydroxy group of the amino acid tyrosine of another protein is. This significantly influences the activity of the target protein, which is why tyrosine kinases also make an important contribution to signal transmission as part of receptor systems.
• Involved in the formation of the glucose transporter GLUT (via signal transmission at the postreceptor level) à Glucose transporters (GLUT, SLC2A) are certain transmembrane transport proteins that catalyze the transport of glucose or fructose through the cell membrane. These are carrier protein-mediated uniports, whereby the concentration gradient of glucose provides the energy required for transport.
• Influences enzymes that regulate glucose utilization
• Also protects against coronary heart disease (lack of oxygen in the heart due to narrowed coronary arteries)
• Typical dosage: 240-900 mg (divided into several doses)

 

Coenzyme Q10

• Diabetes = Q10-consuming disease
  • The majority of diabetics have a Q10 deficiency
  • Increased glycosylation leads to inactivation of many antioxidant enzymes (catalase, superoxide dismutase (SOD))
• Q10 improves metabolic parameters
• Q10 improves blood pressure and blood sugar control
• Q10 important for energy production in the mitochondria (electron transport chain), protection against radicals, membrane stabilization
• Typical dosage: 5-100 mg (depending on the bioavailability of the supplement used)

 

L-Carnitine

• Improvement of glucose metabolism by increasing glycogen synthase activity (with an increase in glucose utilization and a decrease in insulin resistance) and glucose release
• Improvement of diabetic dyslipoproteinemia (increased concentration of triglycerides, reduced levels of “good” HDL cholesterol and a predominance of “bad” LDL cholesterol; this disorder of fat metabolism is the main cause of cardiovascular diseases associated with diabetes)
• Decreases ketone body formation; these occur v.a In type 1 diabetes: If there is a lack of insulin, not enough glucose from the blood reaches the cells, so that fat is burned in the mitochondria instead of sugar.This creates ketone bodies, which in large quantities can lead to ketoacidosis (severe metabolic disorder as a result of hyperacidification caused by ketone bodies).
• Stabilization of nerve cell membranes (improvement in vibration sensation and pain)
• Typical dosage: 200-800 mg/day

 

 

Alpha lipoic acid (contained in Anti-Ox)

• Antioxidant: Reduces lipid peroxidation (includinga in nerve tissue)
• Biocatalyst for energy metabolism (ATP enrichment)
• Inactivates radicals and regenerates vitamin C & E (redox recycling)
• Coenzyme of pyruvate dehydrogenase (catalyzes conversion of pyruvate to acetyl coenzyme A in the mitochondria)
• Prevents protein glycosylation and thus the formation of AGEs
• Inhibits aldose reductase; Aldose reductase (AR) is an enzyme that converts glucose to sorbitol. Because in diabetes mellitus, the AR produces a lot of sorbitol, which accumulates in the cells and especially.a In kidneys, eyes and nerves damage caused by the high osmotic pressure.
• Improves glucose utilization (stimulation of glucose uptake in muscle cells like insulin)
• Increase in glutathione
• Improves polyneuropathy
• Typical dosage: 0.2-1 g

 

Vitamin D

Randomized, controlled, double-blind study with 81 participants over 6 months:
“In insulin-resistant women with vitamin D levels < 50 nmol/l, vitamin D3 100 mcg (4000 IU) significantly reduces insulin resistance. The best results were found with vitamin D levels of 80-119 nmol/l.“
Source: By Hurst PR et al.; Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient – ​​a randomized placebo-controlled trial. British Journal of Nutrition 2009; First view article, doi: 10.1017/S0007114509992017

 

Resveratrol

• Study from 2014: Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. Liu K1, Zhou R1, Wang B1, Mi MT1.
  RESULTS: Eleven studies comprising a total of 388 subjects were included in this meta-analysis. CONCLUSIONS: Resveratrol significantly improves glucose control and insulin sensitivity in persons with diabetes […]. Additional high-quality studies are needed to further evaluate the potential benefits of resveratrol in humans.
• Typical dosage: 500 mg/day