How many people in Germany are affected by diabetes?

Currently, at least 8.7 Millions of people have type 2 diabetes and 32,000 Children and young people as well as 340,000 Adults have type 1 diabetes. Due to pandemic control measures (including lockdowns) in 2020/2021, a significantly increased risk of diabetes in the population is assumed. v.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 consuming carbohydrate-rich foods, blood sugar levels rise, prompting an increased release of insulin. Insulin stimulates fat, liver, and muscle cells to absorb glucose from the blood, thereby lowering blood sugar levels again.

Diabetes mellitus is the umbrella term for metabolic disorders caused by elevated blood sugar levels, resulting from an absolute deficiency or reduced effectiveness of the hormone insulin (relative deficiency). Due to the insulin deficiency, glucose can no longer be absorbed into the cells and therefore cannot be used there as an energy source. Instead, glucose accumulates in the blood.

Above a certain concentration, increased amounts of glucose are excreted via the kidneys/urine, leading to a loss of water and electrolytes.

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

At a absolute insulin deficiency (IDDM) is referred to as Type 1 diabetes, at a relative insulin deficiency or insulin resistance one speaks of Type 2 diabetes (NIDDM), d.hThe target tissues do not respond adequately to released insulin.

Type 1 diabetes

• Absolute insulin deficiency, because the pancreas does not produce enough insulin.
• It is caused by an autoimmune disease in which the body's own immune system destroys the insulin-producing β-cells of the pancreas.
• Begins i.d.R...even in childhood/adolescence
• It is currently incurable, meaning that insulin injections are necessary for the rest of one's life.

Type 2 diabetes

• It arises from reduced sensitivity of body cells to insulin (insulin resistance) as well as from "exhaustion" of the insulin-producing cells in the pancreas due to years of overproduction of insulin.
• Begins i.d.R. creeping and occurred earlier v.aIt occurs in old age (“age-related diabetes”), but is now increasingly also found in young adults and adolescents
• In addition to genetic predisposition v.aThe following risk factors include: lack of exercise, being overweight, an 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 glucose excess in the blood.

What accompanying and secondary diseases occur in diabetes mellitus?

The Diabetes Health Report provides an overview of the Frequency of occurrence of accompanying and subsequent diseases at 120.000 patients with type 2 diabetes under care:

• 75.2% high blood pressure
• 11.9% diabetic retinopathy
• 10.6% neuropathy
• 9.1% heart attack
• 7.4% peripheral arterial occlusive disease (PAOD)
• 4.7% stroke
• 3.3% Nephropathy (kidney failure)
• 1.7% diabetic foot syndrome
• 0.8% amputation
• 0.3% blindness

Oxidative stress is a key cause of many secondary/associated diseases in diabetes mellitus.

All available parameters that are considered indirect measures of oxidative stress (direct measurement is not possible in vivo) are elevated in diabetic patients. Therefore, the formation of free radicals as a consequence of oxidative stress is currently considered a key biochemical explanation for diabetes-associated diseases (see Davi et al., Ceriello et al.).

Elevated blood glucose levels lead to a reaction between sugars and the body's own proteins – a process called glycosylation. This results in the formation of advanced glycation end products (AGEs), which are cross-linked structural proteins that the immune system subsequently attempts to break down. Immune cells, such as macrophages, possess receptors that recognize these AGEs (known as "RAGE"). The glucose-induced increase in blood AGEs leads to an increased production of these receptors, resulting in a macrophage-induced immune response and chronic inflammation. This, in turn, leads to oxidative stress and consequently to vascular damage.

The majority of diabetes-associated diseases arise from pathological changes in smaller cells (microangiopathy --> u.a. Retinopathy, nephropathy, neuropathy) and larger (macroangiopathy) --> v.aAtherosclerosis) blood vessels. In this process, free radicals not only damage cellular membranes, but also lead to changes in the structure and function of the affected vascular cells.

Oxidative phosphorylation, which takes place in the mitochondria, the "powerhouses" of our cells, is also accompanied by the formation of oxygen radicals. When there is an overabundance of glucose, a dysregulation of mitochondrial metabolic processes leads to an increased production of free radicals. Conversely, antioxidant protective enzymes are increasingly glycosylated, thus impairing their function.

Brownlee and colleagues have demonstrated that an overload of vascular cells with substrates such as glucose (hyperglycemia) and fatty acids (hyperlipidemia) increases the mitochondrial electron flow (in the electron transport and respiratory chain) to such an extent that it leads to a massive formation of free radicals. In their studies, they were able to demonstrate both the dependence of radical formation on substrate availability and the partial decoupling of mitochondrial electron flow between complexes II and III of the respiratory chain. Simultaneously, they were able to show that, as a consequence of mitochondrial radical formation, diabetes-specific signaling pathways leading to vascular complications are activated. These include the activation of protein kinase C, the hexosamine pathway, the transcription factors NFκB and SP-1, and the reduced availability of nitric oxide (NO).

Oxidative stress also increases insulin resistance.

Free radicals resulting from oxidative stress and their cytotoxic effects also contribute to the death of β-cells in the pancreas through apoptosis, further impairing insulin synthesis and leading to insulin deficiency. 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 a self-reinforcing system of insulin deficiency and oxidative stress.

Additionally, in diabetes – v.aIn many older patients, a reduced antioxidant capacity contributes to increased oxidative stress, as the supply of antioxidants such as vitamins C, E, coenzyme Q10 or polyphenols such as quercetin, resveratrol, OPC, etc. is often insufficient, especially in old age.

If, on the other hand, oxidative stress is regulated by means of antioxidants, the insulin-dependent glucose uptake by the cells is normalized again (see Klip et al.).

What are the typical risk factors for developing diabetes mellitus?

“Classic” risk factors:

• Metabolic syndrome
  • Lipid metabolism disorder
  • hypertension
  • Overweight/Body fat distribution
• Unhealthy diet (--> oxidative stress)
• Lack of exercise (--> oxidative stress)
• Smoke (--> oxidative stress)

--> Domain of “lifestyle medicine”

Risk factors that can be influenced by micronutrients:

• (chronic) inflammation (“silent inflammation”)
• Hyperhomocysteinemia
• Nitrogen imbalance, elevated ADMA, and relative arginine deficiency
• Mitochondrial dysfunction
• Increased levels of Lp(a), fibrinogen, and plasmin activator
• Disorder of erythrocyte and platelet function
• Stress, depression u.apsychogenic stress
• Oxidative stress = imbalance (free 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 years of type 2 diabetes (insulin production and liver function are normalized) are cured of their disease. Furthermore, it has been known for some time that every second patient who loses 10 kg soon after a diabetes diagnosis recovers.
  (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 July 1, 2011
• High sugar consumption It promotes obesity, type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease (Sources: prospective study of 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" style diet is inexpensive. 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, stroke and heart attack."
  (Source: Prof.) H.P. Meissner, diabetologist, Berlin, ÄP 4.10.2002)
• Of the The American Diabetes Association has officially and explicitly recommended low-carb diets as an option for diabetes therapy since 2020: “...Reducing overall carbohydrate intake for individuals with diabetes 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/dietary supplements are relevant in diabetes mellitus?

Vitamin C

• Vitamin C inhibits the enzyme aldose reductase (AR) and thus the formation of sorbitol. (Aldose reductase is an enzyme that converts glucose to sorbitol). In diabetes mellitus, AR produces a lot of sorbitol, which accumulates in the cells and v.aDamage to the kidneys, eyes, and nerves is caused by the high osmotic pressure.
• Inhibits protein glycosylation (displaces glucose from protein binding sites) and thus the formation of AGEs (with the o.g(negative effects). In cases of vitamin C deficiency, the glycosylation rate is increased!
• Most important water-soluble antioxidant
  • Reduces free radicals resulting from oxidative stress.
  • Does folic acid protect? &Vitamin E before oxidation
• Important for the synthesis of carnitine and neurotransmitters && Collagen
• Lowers insulin resistance and HbA1c (an indicator of blood sugar levels over the last 2-3 months, as it shows the proportion of hemoglobin to which sugar is bound). This is because vitamin C intake increases the concentration of reduced glutathione in the plasma, which alters membrane permeability. This results in improved insulin sensitivity, enabling increased glucose transport into the cell.
• Lowers LDL cholesterolThe 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, allowing it to be broken down unhindered. The concentration of HDL cholesterol, the so-called "good" cholesterol, remains unaffected by the increased vitamin C intake.
• Improves (endothelium-dependent) vasodilation (= widening of blood vessels and thus improvement of blood flow)

Diabetes patients have i.d.RVitamin C deficiency:

• Diabetes patients have at least 30% lower vitamin C levels (Nutr Rev 1996; 57; 193-202)
• HbA1c and vitamin 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 approximately50% reduced storage capacity for vitamin C

Typical dosage: 500-2000 mg (Divided into several portions) over 4 months; the aim is to achieve a level comparable to that of healthy individuals; diabetics need approximately twice as much vitamin C! "To experience 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 supplement, its bioavailability should be considered. With conventional supplements, only a small portion of the ingested vitamin C is actually available to the body, as the absorption rate decreases with increasing dosage, and if the vitamin C blood level rises too quickly or too high, some is excreted 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 and enzymes. && hormones (increased lipid peroxidation in diabetics)
  (through increased glycosylation of plasma proteins)
• Reduces platelet adhesion & -AggregationMayne et al. (1970) and Jäger et al. (1975) demonstrated significantly higher platelet stickiness in diabetics compared to normal subjects.
• Reduces protein glycation and thus AGE formation.
• Reduces thromboxane synthesis (thromboxane activates platelet aggregation)
• Improves the effectiveness of insulin (reduces insulin requirements)
• Reduces the risk of retinopathy and nephropathy
• Reduces fatal heart attacks by 77% (Source: Chaos Study 1996)
• Increased vitamin E requirements in diabetes
• Low vitamin E levels increase the risk of diabetes fourfold.
• Typical dosage: 100-600 mg per day

B vitamins

Possible causes of B vitamin deficiency in diabetes:

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

Relevance of B vitamins in the context of 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 of pain and nerve conduction velocity (B1, B6, B12)
• Regeneration of B cells, formation of glucose tolerance factor (B3) → mediates binding of the
  Insulin at the insulin receptor
• Inhibition of glycation, 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: ideally one high-dose B-complex, because B vitamins activate each other

zinc

Possible causes of zinc deficiency in diabetes:

• Increased zinc excretion via urine (2-3x more)
• Low zinc uptake (z.B(e.g., in the case of a one-sided diet, weight-loss diet)
• Reduced absorption in cases of pancreatic insufficiency, malabsorption, and high-fiber diets (zinc phytate complexes)

Relevance of zinc in relation to diabetes: Reduces NBV &am 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 binding capacity to the insulin receptor
• Does it affect the enzyme carboxypeptidase B (which catalyzes the conversion of proinsulin to 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 deactivating 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
• To be used even before the onset of diabetes (in cases of insulin resistance)
• Tyrosine kinase controls the action of insulin receptors Tyrosine kinases are a group of enzymes from the protein kinase family whose function is the reversible transfer of a phosphate group (phosphorylation) to the hydroxyl group of the amino acid tyrosine of another protein. This significantly influences the activity of the target protein, which is why tyrosine kinases also play an important role in signal transduction as part of receptor systems.
• Involved in the development of the glucose transporter GLUT (via signal transduction at the post-receptor level) à Glucose transporters (GLUT, SLC2A) are specific transmembrane transport proteins that catalyze the transport of glucose or fructose across the cell membrane. They are carrier protein-mediated uniports, with the glucose concentration gradient providing the energy required for transport.
• Affects enzymes that regulate glucose utilization
• It also protects against coronary heart disease. (Lack of oxygen in the heart due to narrowed coronary arteries)
• Typical dosage: 240-900 mg (distributed across several gifts)

Coenzyme Q10

• Diabetes = Q10-consuming disease
  • The majority of diabetics have a Q10 deficiency.
  • Increased glycosylation leads to the inactivation of many antioxidant enzymes (catalase, superoxide dismutase (SOD)).
• Q10 improves metabolic parameters
• Q10 improves blood pressure and blood sugar control
• Q10 is important for energy production in the mitochondria (electron transport chain), protection against radicals, and 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 increased glucose utilization and decreased 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 lipid metabolism is the main cause of cardiovascular diseases associated with diabetes)
• Reduces ketone body formation; these occur v.a. in type 1 diabetes on: If insulin is lacking, not enough glucose from the blood enters the cells, so fat is burned in the mitochondria instead of sugar. This process produces ketone bodies, which in large quantities can lead to ketoacidosis (a severe metabolic disorder resulting from over-acidification due to ketone bodies).
• Stabilization of nerve cell membranes (improvement of vibration perception and pain)
• Typical dosage: 200-800 mg/day

Alpha-lipoic acid (contained in Anti-Ox)

• Antioxidant: Reduces lipid peroxidation (u.a. in nerve tissue)
• Biocatalyst for energy metabolism (ATP enrichment)
• Inactivates free radicals and regenerates vitamin C && E (Redox recycling)
• Coenzyme of pyruvate dehydrogenase (catalyzes the conversion of pyruvate to acetyl-coenzyme A in the mitochondria)
• Prevents protein glycosylation and thus the formation of AGEs
• Inhibits aldose reductaseAldose reductase (AR) is an enzyme that converts glucose to sorbitol. In diabetes mellitus, AR produces a large amount of sorbitol, which accumulates in the cells and... v.a.Damage to the kidneys, eyes and nerves is caused by the high osmotic pressure.
• Improves glucose utilization (Stimulation of glucose uptake into 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 &Vitamin D3 (100 mcg, 4000 IU) significantly reduces insulin resistance at levels below 50 nmol/l. The best results were found at 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