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In Sanskrit, the word mih (from which meha is derived) denotes water, to wet, and to emit semen. Regarding the above explanation, we can easily postulate that the disease prameha resulted because of an excessive excretion of something (ati-pravrittija). Prameha comprises of all those diseases that cause clinical abnormalities in urine due to derangement of metabolism at the level of tissues (dhatvagnimandya).  
 
In Sanskrit, the word mih (from which meha is derived) denotes water, to wet, and to emit semen. Regarding the above explanation, we can easily postulate that the disease prameha resulted because of an excessive excretion of something (ati-pravrittija). Prameha comprises of all those diseases that cause clinical abnormalities in urine due to derangement of metabolism at the level of tissues (dhatvagnimandya).  
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The scope of prameha:
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==== The scope of prameha ====
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Prameha is a complex syndrome encompassing obesity, metabolic syndrome, diabetes insipidus, alkaptonuria, hemoglobinuria, lipiduria, diabetes mellitus and more. At the gross level, prameha is considered an endocrinal and metabolic disorder. Classification of prameha as sahaja (hereditary) and apathyanimittaja (acquired) favors the correlation of madhumeha as diabetes mellitus. The pathological foci of the disease lie in the kidney (vrikka) causing the destruction of nephrons (srotomukh pratirudhyante).  
 
Prameha is a complex syndrome encompassing obesity, metabolic syndrome, diabetes insipidus, alkaptonuria, hemoglobinuria, lipiduria, diabetes mellitus and more. At the gross level, prameha is considered an endocrinal and metabolic disorder. Classification of prameha as sahaja (hereditary) and apathyanimittaja (acquired) favors the correlation of madhumeha as diabetes mellitus. The pathological foci of the disease lie in the kidney (vrikka) causing the destruction of nephrons (srotomukh pratirudhyante).  
    
The classification of prameha on the basis of onset as sahaja/jataja pramehi madhumehi (hereditary) and apathyanimittaja pramehi (acquired) could be considered analogous to the classification of diabetes conditions as congenital/ Type-I, insulin dependent diabetes mellitus (IDDM) and acquired/ Type-II, non insulin-dependent diabetes mellitus (NIDDM) respectively.  
 
The classification of prameha on the basis of onset as sahaja/jataja pramehi madhumehi (hereditary) and apathyanimittaja pramehi (acquired) could be considered analogous to the classification of diabetes conditions as congenital/ Type-I, insulin dependent diabetes mellitus (IDDM) and acquired/ Type-II, non insulin-dependent diabetes mellitus (NIDDM) respectively.  
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Considering the pathogenesis, two types of prameha patients are as given below:  
 
Considering the pathogenesis, two types of prameha patients are as given below:  
 
a. Sahaja prameha/ jatah pramehi (hereditary)
 
a. Sahaja prameha/ jatah pramehi (hereditary)
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1. A certain defect in the sperm and ovum (referred to as bija dosha) results in a genetic disorder or genetic predisposition to disease. Regarding prameha, Charaka Samhita mentions that excessive indulgence in madhura rasa (foods/ drinks with a sweet taste) by the parents is the chief cause of this chromosomal damage to the sperm and ovum.
 
1. A certain defect in the sperm and ovum (referred to as bija dosha) results in a genetic disorder or genetic predisposition to disease. Regarding prameha, Charaka Samhita mentions that excessive indulgence in madhura rasa (foods/ drinks with a sweet taste) by the parents is the chief cause of this chromosomal damage to the sperm and ovum.
 
2. An intrauterine environment that negatively affects the development of the fetus due to the mother’s diet, lifestyle, or adverse psychologic state during pregnancy. This congenital aspect can trigger the disease process for which there is a genetic predisposition. Regarding prameha, the overindulgence of madhura rasa by the mother during pregnancy is likely to trigger prameha.
 
2. An intrauterine environment that negatively affects the development of the fetus due to the mother’s diet, lifestyle, or adverse psychologic state during pregnancy. This congenital aspect can trigger the disease process for which there is a genetic predisposition. Regarding prameha, the overindulgence of madhura rasa by the mother during pregnancy is likely to trigger prameha.
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The diet, lifestyle, and adverse psychologic state of the mother during lactation (and only during the stage of pregnancy)may also play a decisive role in precipitating prameha in the infants. In addition, excessive intake of madhura rasa during childhood can contribute to the onset of prameha in children who are genetically predisposed. Thus, hereditary predisposition and unwholesome dietary and lifestyle choices, especially excessive intake of madhura rasa, can play a combined role to cause hereditary prameha. The description of sahaja prameha in Sushruta Samhita and jatah prameha  in Charaka Samhita are quite similar to that of type-I diabetes (also known as insulin- dependent diabetes mellitus or juvenile- onset diabetes). Jatah pramehi madhumehino, as defined in Charaka Samhita, correlates with type-I diabetes beginning in early childhood.
 
The diet, lifestyle, and adverse psychologic state of the mother during lactation (and only during the stage of pregnancy)may also play a decisive role in precipitating prameha in the infants. In addition, excessive intake of madhura rasa during childhood can contribute to the onset of prameha in children who are genetically predisposed. Thus, hereditary predisposition and unwholesome dietary and lifestyle choices, especially excessive intake of madhura rasa, can play a combined role to cause hereditary prameha. The description of sahaja prameha in Sushruta Samhita and jatah prameha  in Charaka Samhita are quite similar to that of type-I diabetes (also known as insulin- dependent diabetes mellitus or juvenile- onset diabetes). Jatah pramehi madhumehino, as defined in Charaka Samhita, correlates with type-I diabetes beginning in early childhood.
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(Note: Glycemic Index is a unit which measures the amount of glucose released into the blood by a food source. Foods which release more glucose into the blood will have a high glycemic Index value and vice versa.)
 
(Note: Glycemic Index is a unit which measures the amount of glucose released into the blood by a food source. Foods which release more glucose into the blood will have a high glycemic Index value and vice versa.)
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The classification of prameha:
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==== The classification of prameha ====
    
a) Classification by Dosha/Stage of Progression
 
a) Classification by Dosha/Stage of Progression
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Prameha classified according to physique:
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==== Prameha classified according to physique ====
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  In Ayurveda, much emphasis has been given to the role of meda in the pathogenesis of prameha. However, its role is not only as a dushya (disturbed functioning of the dhatus), but something more than that. Bahudrava shleshma (kapha that contains too much liquid) joins and affects meda, causing it to become abadha (unobstructed or fluid) in nature. This form of meda has been described to have an effect on mamsa (muscle tissue), thereby increasing the volume of body fluid. This has been described as sharira- kleda (body fluid). This route of pathogenesis for prameha is closely related to obesity.  
 
  In Ayurveda, much emphasis has been given to the role of meda in the pathogenesis of prameha. However, its role is not only as a dushya (disturbed functioning of the dhatus), but something more than that. Bahudrava shleshma (kapha that contains too much liquid) joins and affects meda, causing it to become abadha (unobstructed or fluid) in nature. This form of meda has been described to have an effect on mamsa (muscle tissue), thereby increasing the volume of body fluid. This has been described as sharira- kleda (body fluid). This route of pathogenesis for prameha is closely related to obesity.  
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Samprapti (pathogenesis) of prameha
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==== Samprapti (pathogenesis) of prameha ====
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The scientific utility of this chapter lies in the fact that in prameha the vitiated kapha first vitiates meda dhatu followed by mamsa and other dushya and then finally vitiates mutra to manifest as prameha. This signifies that hyperglycemia is preceded by dyslipidiemias. One more interesting fact is that the main culprit of the disease i.e. kapha is inherently denatured, means it looses its natural properties due to hereditary defect what we know today as genetic susceptability. Furthermore, it is added that if a disease appeared due to genetic default, then it is incurable. A step ahead from the present contemporary knowledge, it is mentioned that as genetic modulation can cause disease similarly a chronic disease can cause gene modulation and vice-versa.   
 
The scientific utility of this chapter lies in the fact that in prameha the vitiated kapha first vitiates meda dhatu followed by mamsa and other dushya and then finally vitiates mutra to manifest as prameha. This signifies that hyperglycemia is preceded by dyslipidiemias. One more interesting fact is that the main culprit of the disease i.e. kapha is inherently denatured, means it looses its natural properties due to hereditary defect what we know today as genetic susceptability. Furthermore, it is added that if a disease appeared due to genetic default, then it is incurable. A step ahead from the present contemporary knowledge, it is mentioned that as genetic modulation can cause disease similarly a chronic disease can cause gene modulation and vice-versa.   
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Various dushyas involved in the pathogenesis:
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Various dushyas involved in the pathogenesis:
 
Medadhatu :  
 
Medadhatu :  
 
Meda vitiation is common and dominant dushya in the pathogenesis of madhumeha. Kapha and meda both have close resemblance in regard to functions as well as in regard to qualitative parameters. Both get vitiated more or less by same etiological factors. In madhumeha vitiation of meda results by two ways:   
 
Meda vitiation is common and dominant dushya in the pathogenesis of madhumeha. Kapha and meda both have close resemblance in regard to functions as well as in regard to qualitative parameters. Both get vitiated more or less by same etiological factors. In madhumeha vitiation of meda results by two ways:   
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Vataja prameha as type 1 diabetes mellitus : The pathogenesis of vataja prameha is similar to that of type-1 diabetes mellitus. Vata is agitated due to various precipitating causes acts on the body in such a way that there is passage of vasa (fat), majja (bone marrow), lasika (lymph), and ojas (essence of the body /immune substances / vitality) through the urine. This condition indicates impaired renal function as a result of diabetes, leading to a dire prognosis. Due to dhatukshaya (loss of body tissues) the patient become very weak and emaciated.
 
Vataja prameha as type 1 diabetes mellitus : The pathogenesis of vataja prameha is similar to that of type-1 diabetes mellitus. Vata is agitated due to various precipitating causes acts on the body in such a way that there is passage of vasa (fat), majja (bone marrow), lasika (lymph), and ojas (essence of the body /immune substances / vitality) through the urine. This condition indicates impaired renal function as a result of diabetes, leading to a dire prognosis. Due to dhatukshaya (loss of body tissues) the patient become very weak and emaciated.
 
Charaka Samhita deals with very specific pathogenesis for madhumeha, which is a subtype of vataja prameha. When an individual excessively consumes the foods that cause prameha, kapha and pitta become vitiated, then adipose tissues and muscle tissuses become disturbed and causes impaired functioning of vata. Subsequently vata gets vitiated and extends to urinary bladder along with ojas, resulting in ojas being expelled in the urine. In Ayurveda ojas is considered vital to the maintanence of health; its loss in prameha leads to many complications, including prameha pidika (boils and carbuncles). This advanced condition is comparable to non-insulin –dependent type -2 diabetes progressing into insulin dependent diabetes. It is the stage of diabetes in which there are complications, including nephropathy, which result in vital substances of the body being excreted through urine.
 
Charaka Samhita deals with very specific pathogenesis for madhumeha, which is a subtype of vataja prameha. When an individual excessively consumes the foods that cause prameha, kapha and pitta become vitiated, then adipose tissues and muscle tissuses become disturbed and causes impaired functioning of vata. Subsequently vata gets vitiated and extends to urinary bladder along with ojas, resulting in ojas being expelled in the urine. In Ayurveda ojas is considered vital to the maintanence of health; its loss in prameha leads to many complications, including prameha pidika (boils and carbuncles). This advanced condition is comparable to non-insulin –dependent type -2 diabetes progressing into insulin dependent diabetes. It is the stage of diabetes in which there are complications, including nephropathy, which result in vital substances of the body being excreted through urine.
  Among patients with significant proteinuria, the degeneration of cells within epithelial casts may result in a characteristic "Maltese cross" appearance and a fatty cast. These droplets are composed of cholesterol esters and cholesterol, which may also be observed free in the urine. This may be correlated with vasameha (lipiduria). Majjameha can be correlated with appearance of waxy casts in urine in advanced renal failure.  Waxy cast are thought to be the last stage of the degeneration of a granular cast. Since this degenerative process is probably slow, it is most likely observed in nephrons with much diminished flow. Waxy casts are therefore most consistent with the presence of advanced renal failure.   
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Among patients with significant proteinuria, the degeneration of cells within epithelial casts may result in a characteristic "Maltese cross" appearance and a fatty cast. These droplets are composed of cholesterol esters and cholesterol, which may also be observed free in the urine. This may be correlated with vasameha (lipiduria). Majjameha can be correlated with appearance of waxy casts in urine in advanced renal failure.  Waxy cast are thought to be the last stage of the degeneration of a granular cast. Since this degenerative process is probably slow, it is most likely observed in nephrons with much diminished flow. Waxy casts are therefore most consistent with the presence of advanced renal failure.   
 
Hastimeha can be correlated with polyuria in diabetic ketoacidosis due to osmotic dieresis and electrolyte imbalance. Insidious increased thirst (i.e. polydipsia) and urination (i.e. polyuria) are the most common early symptoms of diabetic ketoacidosis (DKA).  
 
Hastimeha can be correlated with polyuria in diabetic ketoacidosis due to osmotic dieresis and electrolyte imbalance. Insidious increased thirst (i.e. polydipsia) and urination (i.e. polyuria) are the most common early symptoms of diabetic ketoacidosis (DKA).  
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Causes of lipoprotein abnormalities in diabetes:  Defects in insulin action and hyperglycemia could lead to changes in plasma lipoproteins in patients with diabetes. Alternatively, especially in the case of type 2 diabetes, the obesity/insulin-resistant metabolic disarray that is at the root of this form of diabetes could, itself, lead to lipid abnormalities exclusive of hyperglycemia.  
 
Causes of lipoprotein abnormalities in diabetes:  Defects in insulin action and hyperglycemia could lead to changes in plasma lipoproteins in patients with diabetes. Alternatively, especially in the case of type 2 diabetes, the obesity/insulin-resistant metabolic disarray that is at the root of this form of diabetes could, itself, lead to lipid abnormalities exclusive of hyperglycemia.  
 
The lipoprotein abnormalities commonly present in type 2 diabetes, previously termed noninsulin-dependent diabetes mellitus, include hypertriglyceridemia and reduced plasma HDL cholesterol. In addition, low density lipoprotein (LDL) are converted to smaller, perhaps more atherogenic, lipoproteins termed small dense LDL. In contrast to type 1 diabetes, this phenotype is not usually fully corrected with glycemic control. Moreover, this dyslipidemia often is found in prediabetics, patients with insulin resistance but normal indexes of plasma glucose. Therefore, abnormalities in insulin action and not hyperglycemia per se are associated with this lipid abnormality. Several factors are likely to be responsible for diabetic dyslipidemia: insulin effects on liver apoprotein production, regulation of lipoprotein lipase (LpL), actions of cholesteryl ester transfer protein (CETP), and peripheral actions of insulin on adipose and muscle.  
 
The lipoprotein abnormalities commonly present in type 2 diabetes, previously termed noninsulin-dependent diabetes mellitus, include hypertriglyceridemia and reduced plasma HDL cholesterol. In addition, low density lipoprotein (LDL) are converted to smaller, perhaps more atherogenic, lipoproteins termed small dense LDL. In contrast to type 1 diabetes, this phenotype is not usually fully corrected with glycemic control. Moreover, this dyslipidemia often is found in prediabetics, patients with insulin resistance but normal indexes of plasma glucose. Therefore, abnormalities in insulin action and not hyperglycemia per se are associated with this lipid abnormality. Several factors are likely to be responsible for diabetic dyslipidemia: insulin effects on liver apoprotein production, regulation of lipoprotein lipase (LpL), actions of cholesteryl ester transfer protein (CETP), and peripheral actions of insulin on adipose and muscle.  
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Different solours of Urine:
 
Different solours of Urine:
 
White colour Urine:  
 
White colour Urine:  
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• Urinary hydroxyphenylpyruvic acid excretion due the metabolic disorder tyrosinosis will also cause urine to be brown-black in color.
 
• Urinary hydroxyphenylpyruvic acid excretion due the metabolic disorder tyrosinosis will also cause urine to be brown-black in color.
 
• In porphyria cutanea tarda, the urine will appear reddish brown in natural light but fluoresces pink under ultraviolet light.
 
• In porphyria cutanea tarda, the urine will appear reddish brown in natural light but fluoresces pink under ultraviolet light.
Prognosis:
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==== Prognosis ====
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On the basis of prognosis, patients of prameha have been classified into three groups: Sadhya (curable), Yapya (controllable), and Asadhya (difficult to manage).
 
On the basis of prognosis, patients of prameha have been classified into three groups: Sadhya (curable), Yapya (controllable), and Asadhya (difficult to manage).
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                                         fatty acid metabolism
 
                                         fatty acid metabolism
 
                                           Hyperinsulinemia   
 
                                           Hyperinsulinemia   
Future Scope for Research:
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=== Future Scope for Research ===
 
1. Assessment criteria for the classification of various types of Prameha based on both physical as well as laboratory parameters.
 
1. Assessment criteria for the classification of various types of Prameha based on both physical as well as laboratory parameters.
 
2.  Scaling the Prameha on the basis of modern investing tools so that the management can be done on the basis of classification.
 
2.  Scaling the Prameha on the basis of modern investing tools so that the management can be done on the basis of classification.
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6.  Retroprospective clinical study to establish the fact that dyslipidemia is the cause of diabetes and not the consequence of diabetes.
 
6.  Retroprospective clinical study to establish the fact that dyslipidemia is the cause of diabetes and not the consequence of diabetes.
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Glossary of Tecchnical Terms:
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=== Glossary of Tecchnical Terms ===
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1. विकाराभिनिर्वृत्तिः vikArAbhinirvRuttiH-  Appearance of disease
 
1. विकाराभिनिर्वृत्तिः vikArAbhinirvRuttiH-  Appearance of disease
 
2. चिराद्वाऽप्यभिनिर्वर्तन्ते,cirAdvA~apyabhinirvartante- delayed appearance of disease or increased incubation period  
 
2. चिराद्वाऽप्यभिनिर्वर्तन्ते,cirAdvA~apyabhinirvartante- delayed appearance of disease or increased incubation period  
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45. Sahajapramehi- Congenital, hereditary diabetes mellitus. The term signifies diabetes mellitus due to hereditary or congenital causes.
 
45. Sahajapramehi- Congenital, hereditary diabetes mellitus. The term signifies diabetes mellitus due to hereditary or congenital causes.
 
46. Lasikävatmütram- Urine resembling lymph The term signifies urination resembling lymph in characteristics.
 
46. Lasikävatmütram- Urine resembling lymph The term signifies urination resembling lymph in characteristics.
References: